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Sample records for beta-adrenergic receptor population

  1. Beta adrenergic receptors in human cavernous tissue

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    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  2. Changes of lymphocyte beta-adrenergic receptors after surgical stress.

    Science.gov (United States)

    Eandi, M; Buraglio, M; Arduino, C; Viano, I; Sansalvadore, G; Arbinolo, M A

    1984-01-01

    In this study the authors' purpose was to observe the effects of surgical stress on the number of lymphocyte beta-adrenergic receptors in hypertensive and normotensive subjects. It was noticed that after surgery a significant reduction occurred in the number of binding sites of lymphocytes of both hypertensive and normotensive subjects. The time course of recovery to the pre-operative values of binding sites varied between the two groups, being slower in normotensive than in hypertensive patients. This might suggest a different pattern of regulation of the beta-adrenergic receptor between hypertensive and normotensive subjects.

  3. Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

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    Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

    1989-06-01

    The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of (125I)cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.

  4. Effect of electrical stimulation on beta-adrenergic receptor population and cyclic amp production in chicken and rat skeletal muscle cell cultures

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.; Strietzel, C. J.

    2000-01-01

    Expression of the beta-adrenergic receptor (betaAR) and its coupling to cyclic AMP (cAMP) synthesis are important components of the signaling system that controls muscle atrophy and hypertrophy, and the goal of this study was to determine if electrical stimulation in a pattern simulating slow muscle contraction would alter the betaAR response in primary cultures of avian and mammalian skeletal muscle cells. Specifically, chicken skeletal muscle cells and rat skeletal muscle cells that had been grown for 7 d in culture were subjected to electrical stimulation for an additional 2 d at a pulse frequency of 0.5 pulses/sec and a pulse duration of 200 msec. In chicken skeletal muscle cells, the betaAR population was not significantly affected by electrical stimulation; however, the ability of these cells to synthesize cyclic AMP was reduced by approximately one-half. In contrast, the betaAR population in rat muscle cells was increased slightly but not significantly by electrical stimulation, and the ability of these cells to synthesize cyclic AMP was increased by almost twofold. The basal levels of intracellular cyclic AMP in neither rat muscle cells nor chicken muscle cells were affected by electrical stimulation.

  5. Electrical Stimulation Decreases Coupling Efficiency Between Beta-Adrenergic Receptors and Cyclic AMP Production in Cultured Muscle Cells

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.

    1999-01-01

    Electrical stimulation of skeletal muscle cells in culture is an effective way to simulate the effects of muscle contraction and its effects on gene expression in muscle cells. Expression of the beta-adrenergic receptor and its coupling to cyclic AMP synthesis are important components of the signaling system that controls muscle atrophy and hypertrophy, and the goal of this project was to determine if electrical stimulation altered the beta-adrenergic response in muscle cells. Chicken skeletal muscle cells that had been grown for seven days in culture were subjected to electrical stimulation for an additional two days at a pulse frequency of 0.5 pulses/sec and a pulse duration of 200 msec. At the end of this two-day stimulation period, beta-adrenergic receptor population was measured by the binding of tritium-labeled CGP-12177 to muscle cells, and coupling to cAMP synthesis was measured by Radioimmunoassay (RIA) after treating the cells for 10 min with the potent (beta)AR agonist, isoproterenol. The number of beta adrenergic receptors and the basal levels of intracellular cyclic AMP were not affected by electrical stimulation. However, the ability of these cells to synthesize cyclic AMP was reduced by approximately 50%. Thus, an enhanced level of contraction reduces the coupling efficiency of beta-adrenergic receptors for cyclic AMP production.

  6. Brain beta-adrenergic receptor binding in rats with obesity induced by a beef tallow diet.

    Science.gov (United States)

    Matsuo, T; Suzuki, M

    1997-01-01

    We have previously reported that compared with safflower oil diet, feeding a beef tallow diet leads to a greater accumulation of body fat by reducing sympathetic activities. The present study examined the effects of dietary fats consisting of different fatty acids on alpha1- and beta-adrenergic receptor binding in the hypothalamus and cerebral cortex. Male Sprague-Dawley rats were meal-fed isoenergetic diets based on safflower oil (rich in n-6 polyunsaturated fatty acids) or beef tallow (rich in saturated fatty acids) for 8 weeks. Binding affinities of the beta-adrenergic receptor in the hypothalamus and cortex were significantly lower in the beef tallow diet group, but those of the alpha1-receptor did not differ between the two groups. The polyunsaturated to saturated fatty acid (P/S) ratio and fluidities of plasma membranes in the hypothalamus and cortex were lower in the beef tallow diet group than in the safflower oil diet group. These results suggest that the beef tallow diet decreases membrane fluidity by altering the fatty acid composition of plasma membranes in the hypothalamus and cerebral cortex of rat. Consequently, beta-adrenergic receptor binding affinities in the brain were lower in rats fed the beef tallow diet than in rats fed the safflower oil diet. We recognized that there is possible link between the membrane fluidity and the changes in affinity of beta-adrenoceptors in rat brain.

  7. Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AM Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.; Wuethrich, A. J.; Hancock, D. L.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Broiler chickens at 35 days of age were fed 1 ppm clenbuterol for 14 days. This level of dietary clenbuterol led to 5-7% increases in weights of leg and breast muscle tissue. At the end of the 14-day period, serum was prepared from both control and clenbuterol-treated chickens and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and breast muscle groups of twelve-day chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 micron clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 days beginning on the seventh day in culture. Neither the percent fusion nor the number of nuclei in myotubes were significantly affected by any of the treatments. The quantity of MHC was not increased by serum from clenbuterol-treated chickens in either breast and leg muscle cultures; however, MHC quantity was 50- 100% higher in cultures grown in control chicken serum to which 10 nM and 50 nM clenbuterol had also been added. The Beta-AR population was 4,000-7,000 Beta-AR per cell in cultures grown in chicken serum, with leg muscle cultures having approximately 25-30% more receptors than breast muscle cultures. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the Beta-AR population in leg and breast muscle cultures grown in the presence of 10% horse serum was 18,000-20,000 Beta-AR per cell. Basal concentration of cAMP was not significantly affected by any of the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 micron isoproterenol, limited increases of 12-20% in cAMP concentration above basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 micron isoproterenol, increases of 600

  8. Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AMP Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

    Science.gov (United States)

    Young, Ronald B.; Bridge, Kristin Y.; Wuethrich, Andrew J.; Hancock, Deana L.

    2002-01-01

    Broiler chickens at 35 d of age were fed 1 ppm clenbuterol for 14 d. This level of dietary clenbuterol led to 5-7% increases in the weights of leg and breast muscle tissue. At the end of the 14-d period, serum was prepared from both control and clenbuterol-treated chickens, and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and the breast muscle groups of 12-d chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 uM clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 d, beginning on the seventh d in culture. Neither the percent fusion nor the number of nuclei in myotubes was significantly affected by any of the treatments. The quantity of myosin heavy chains (MHCs) was not increased by serum from clenbuterol-treated chickens in either breast or leg muscle cultures; however, the MHC quantity was 50-150% higher in cultures grown in control chicken serum to which 10 and 50 nM clenbuterol had also been added. The B-adrenergic receptor (betaAR) population was 4000-7000 betaARs per cell in cultures grown in chicken serum with leg muscle cultures having approximately 25-30% more receptors than breast muscle Culture. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the betaAR Population in leg and breast muscle cultures grown in the presence of 10% horse serum was 16,000-18,000 betaARs per cell. Basal concentration of cyclic adenosine 3':5'monophosphate (cAMP) was not significantly affected by the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 uM isoproterenol, limited increases of 12-20% in cAMP Concentration above the. basal levels were observed. However, when cultures grown in the presence of horse serum were

  9. Beta-Adrenergic Receptor Population is Up-Regulated by Increased Cyclic Amp Concentration in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, Ronald B.; Bridge, Kristin Y.; Vaughn, Jeffrey R.

    1999-01-01

    Skeletal muscle hypertrophy is promoted in vivo by administration of beta-drenergic receptor (bAR) agonists. Chicken skeletal muscle cells were treated with 1 (mu)M isoproterenol, a strong bAR agonist, between days 7 and 10 in culture. bAR population increased by approximately 40% during this treatment; however, the ability of the cells to synthesize cyclic AMP (cAMP) was diminished by two-fold. The quantity of myosin heavy chain (MHC) was not affected. To understand further the relationship between intracellular cAMP levels, bAR population, and muscle protein accumulation, intracellular cAMP levels were artificially elevated by treatment with 0-10 uM forskolin for up to three days. The basal concentration of CAMP in forskolin-treated cells increased up to 7-fold in a dose dependent manner. Increasing concentrations of forskolin also led to an increase in bAR population, with a maximum increase of approximately 40-60% at 10 uM forskolin. A maximum increase of 40-50% in the quantity of MHC was observed at 0.2 uM forskolin, but higher concentrations of forskolin reduced the quantity of MHC back to control levels. At 0.2 uM forskolin, intracellular levels of cAMP were higher by approximately 35%, and the (beta)AR population was higher by approximately 30%. Neither the number of muscle nuclei fused into myotubes nor the percentage of nuclei in myotubes were affected by forskolin at any of the concentrations studied.

  10. Characterization of beta-adrenergic receptors in dispersed rat testicular interstitial cells

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    Poyet, P.; Labrie, F.

    1987-01-01

    Recent studies have shown that beta-adrenergic agents stimulate steroidogenesis and cyclic AMP formation in mouse Leydig cells in culture. To obtain information about the possible presence and the characteristics of a beta-adrenergic receptor in rat testicular interstitial cells, the potent beta-adrenergic antagonist (/sup 125/I)cyanopindolol (CYP) was used as ligand. Interstitial cells prepared by collagenase dispersion from rat testis were incubated with the ligand for 2 h at room temperature. (/sup 125/I)cyanopindolol binds to a single class of high affinity sites at an apparent KD value of 15 pM. A number of sites of 6,600 sites/cell is measured when 0.1 microM (-) propranolol is used to determine non-specific binding. The order of potency of a series of agonists competing for (/sup 125/I)cyanopindolol binding is consistent with the interaction of a beta 2-subtype receptor: zinterol greater than (-) isoproterenol greater than (-) epinephrine = salbutamol much greater than (-) norepinephrine. In addition, it was observed that the potency of a large series of specific beta 1 and beta 2 synthetic compounds for displacing (/sup 125/I)cyanopindolol in rat interstitial cells is similar to the potency observed for these compounds in a typical beta 2-adrenergic tissue, the rat lung. For example, the potency of zinterol, a specific beta 2-adrenergic agonist, is 10 times higher in interstitial cells and lung than in rat heart, a typical beta 1-adrenergic tissue. Inversely, practolol, a typical beta 1-antagonist, is about 50 times more potent in rat heart than in interstitial cells and lung.

  11. Determination of beta-adrenergic receptor blocking pharmaceuticals in united states wastewater effluent

    Energy Technology Data Exchange (ETDEWEB)

    Huggett, D.B.; Khan, I.A.; Foran, C.M.; Schlenk, D

    2003-02-01

    This is the first report of beta-adrenergic receptor antagonist pharmaceuticals in United States wastewater effluent. - Beta adrenergic receptor antagonists ({beta}-Blockers) are frequently prescribed medications in the United States and have been identified in European municipal wastewater effluent, however no studies to date have investigated these compounds in United States wastewater effluent. Municipal wastewater effluent was collected from treatment facilities in Mississippi, Texas, and New York to investigate the occurrence of metoprolol, nadolol, and propranolol. Propranolol was identified in all wastewater samples analyzed (n=34) at concentrations {<=}1.9 {mu}g/l. Metoprolol and nadolol were identified in {>=}71% of the samples with concentrations of metoprolol {<=}1.2 {mu}g/l and nadolol {<=}0.36 {mu}g/l. Time course studies at both Mississippi plants and the Texas plant indicate that concentrations of propranolol, metoprolol, and nadolol remain relatively constant at each sampling period. This study indicates that {beta}-Blockers are present in United States wastewater effluent in the ng/l to {mu}g/l range.

  12. Synthesis of the sup 11 C-labelled. beta. -adrenergic receptor ligands atenolol, metoprolol and propanolol

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    Antoni, G.; Ulin, J.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

    1989-01-01

    The {sup 11}C-labelled {beta}-adrenergic receptor ligands atenolol 1, metoprolol 2 and propranolol 3 have been synthesized by an N-alkylation reaction using (2-{sup 11}C)isopropyl iodide. The labelled isopropyl iodide was prepared in a one-pot reactor system from ({sup 11}C)carbon dioxide and obtained in 40% radiochemical yield within 14 min reaction time. The total reaction times for compounds 1-3, counted from the start of the isopropyl iodide synthesis and including purification were 45-55 min. The products were obtained in 5-15% radiochemical yields and with radiochemical purities higher than 98%. The specific activity ranged from 0.4 to 4 GBq/{mu}mol. In a typical experiment starting with 4 GBq around 75 MBq of product was obtained. (author).

  13. Ischemia- and agonist-induced changes in. alpha. - and. beta. -adrenergic receptor traffic in guinea pig hearts

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    Maisel, A.S.; Motulsky, H.J.; Ziegler, M.G.; Insel, P.A. (Univ. of California, La Jolla (USA))

    1987-11-01

    The authors have used radioligand binding techniques and subcellular fraction to assess whether changes in expression of myocardial {alpha}{sub 1}- and {beta}-adrenergic receptors are mediated by a redistribution of receptors between various membrane fractions. Three fractions were prepared from the left ventricles of guinea pigs that underwent either 1 h of ischemia or injection of epinephrine a crude membrane, a purified sarcolemma, and a light vesicle fraction. In control animals {alpha}{sub 1}-adrenergic receptors (({sup 3}H)prazosin binding) in light vesicles was only 25% of the total {alpha}{sub 1}-receptor density found in sarcolemmal and light vesicle fractions as compared with 50% for {beta}-adrenergic receptors (({sup 125}I)iodocyanopindolol binding sites). Although ischemia was associated with a 53% decrease in the number of light vesicle {beta}-adrenergic receptors and a 42% increase in the number of sarcolemma {beta}-receptors there was no change in the number of light vesicle {alpha}{sub 1}-receptors, even though the number of sarcolemmal {alpha}{sub 1}-receptors increased 34%. Epinephrine treatment promoted internalization of {beta}-adrenergic receptors. These results indicate that {alpha}{sub 1} and {beta}{sub 1}-adrenergic receptors may undergo a different cellular itinerary in guinea pig myocardium. Agonist and ischemia-induced changes in surface {beta}-receptors, but not {alpha}{sub 1}-receptors, appear to result from entry and exit of receptors from an intracellular pool that can be isolated in a light vesicle fraction. Changes in expression of {alpha}{sub 1}-adrenergic receptors may represent changes in the properties of receptors found in the sarcolemma or in a membrane fraction other than the light vesicle fraction that they have isolated.

  14. Altered beta-adrenergic receptor-stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors.

    Science.gov (United States)

    Huang, H M; Gibson, G E

    1993-07-15

    An alteration in signal transduction systems in Alzheimer's disease would likely be of pathophysiological significance, because these steps are critical to normal brain function. Since dynamic processes are difficult to study in autopsied brain, the current studies utilized cultured skin fibroblasts. The beta-adrenergic-stimulated increase in cAMP was reduced approximately 80% in fibroblasts from Alzheimer's disease compared with age-matched controls. The deficit in Alzheimer fibroblasts in response to various adrenergic agonists paralleled their beta-adrenergic potency, and enhancement of cAMP accumulation by a non-adrenergic agonist, such as prostaglandin E1, was similar in Alzheimer and control fibroblasts. Diminished adenylate cyclase activity did not underlie these abnormalities, since direct stimulation of adenylate cyclase by forskolin elevated cAMP production equally in Alzheimer and control fibroblasts. Cholera toxin equally stimulated cAMP formation in Alzheimer and control fibroblasts. Moreover, cholera toxin partially reduced isoproterenol-induced cAMP deficit in Alzheimer fibroblasts. Pertussis toxin, on the other hand, did not alter the Alzheimer deficits. The results suggest either that the coupling of the GTP-binding protein(s) to the beta-adrenergic receptor is abnormal or that the sensitivity of receptor is altered with Alzheimer's disease. Further, any hypothesis about Alzheimer's disease must explain why a reduced beta-adrenergic-stimulated cAMP formation persists in tissue culture.

  15. Immunoanalogue of vertebrate beta-adrenergic receptor in the unicellular eukaryote Paramecium.

    Science.gov (United States)

    Wiejak, Jolanta; Surmacz, Liliana; Wyroba, Elzbieta

    2002-01-01

    Cell fractionation, SDS-PAGE, quantitative Western blot, confocal immunolocalization and immunogold labelling were performed to find an interpretation of the physiological response of the unicellular eukaryote Paramecium to beta-adrenergic ligands. The 69 kDa polypeptide separated by SDS-PAGE in S2 and P2 Paramecium subcellular fractions cross-reacted with antibody directed against human beta2-adrenergic receptor. This was detected by Western blotting followed by chemiluminescent detection. Quantitative image analysis showed that beta-selective adrenergic agonist (-)-isoproterenol--previously shown to enhance phagocytic activity--evoked redistribution of the adrenergic receptor analogue from membraneous (P2) to cytosolic (S2) fraction. The relative increase in immunoreactive band intensity in S2 reached 80% and was paralleled by a 59% decrease in P2 fraction. Confocal immunofluorescence revealed beta2-adrenergic receptor sites on the cell surface and at the ridge of the cytopharynx--where nascent phagosomes are formed. This localization was confirmed by immunoelectron microscopy. These results indicate that the 69 kDa Paramecium polypeptide immunorelated to vertebrate beta2-adrenergic receptor appeared in this evolutionary ancient cell as a nutrient receptor.

  16. Age-associated alterations in hepatic. beta. -adrenergic receptor/adenylate cyclase complex

    Energy Technology Data Exchange (ETDEWEB)

    Graham, S.M.; Herring, P.A.; Arinze, I.J.

    1987-09-01

    The effect of age on catecholamine regulation of hepatic glycogenolysis and on hepatic adenylate cyclase was studied in male rats up to 24 mo of age. Epinephrine and norepinephrine stimulated glycogenolysis in isolated hepatocytes at all age groups studied. Isoproterenol, however, stimulated glycogenolysis only at 24 mo. In isolated liver membranes, usual activators of adenylate cyclase increased the activity of the enzyme considerably more in membranes from 24-mo-old rats than in membranes from either 3- or 22-mo-old rats. The Mn/sup 2 +/-dependent activity of the cyclase was increased by 2.9-fold in 3-mo-old animals and approx. 5.7-fold in 24-mo-old rats, indicating a substantial age-dependent increase in the intrinsic activity of the catalytic unit. The density of the ..beta..-adrenergic receptor, as measured by the binding of (/sup 125/I)-iodocyanopindolol to plasma membranes, was 5-8 fmol/mg protein in rats aged 3-12 mo but increased to 19 fmol/mg protein in 24-mo-old rats. Computer-aided analysis of isoproterenol competition of the binding indicated a small age-dependent increase in the proportion of ..beta..-receptors in the high-affinity state. These observations suggest that ..beta..-receptor-mediated hepatic glycogenolysis in the aged rat is predicated upon increases in the density of ..beta..-receptors as well as increased intrinsic activity of the catalytic unit of adenylate cyclase.

  17. Pregnancy modifies the alpha2-beta-adrenergic receptor functional balance in rabbit fat cells.

    Science.gov (United States)

    Bousquet-Mélou, A; Muñoz, C; Galitzky, J; Berlan, M; Lafontan, M

    1999-02-01

    The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: beta1, beta2, beta3, and alpha2. During pregnancy, maternal metabolism presents anabolic and catabolic phases, characterized by modifications of fat responsiveness to catecholamines. The contributions of the four adrenergic receptors to adipocyte responsiveness during pregnancy have never been studied. Our aim was to evaluate the influence of pregnancy on adrenergic receptor-mediated lipolysis in rabbit white adipocytes. Functional studies were performed using subtype-selective and non-selective adrenergic receptor agonists. Overall adrenergic responsiveness was measured with the physiological agonist epinephrine. Non-adrenergic agents were used to evaluate different steps of the lipolytic cascade. The alpha2- and beta1/beta2-adrenergic receptor numbers were determined with selective radioligands. Non-adrenergic agents revealed that pregnancy induced an intracytoplasmic modification of the lipolytic cascade in inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in beta1- and specially beta3-mediated lipolysis. The amounts of adipocyte beta1/beta2- and alpha2-adrenergic receptors were increased in pregnant rabbits. Epinephrine effects revealed an increased contribution of alpha2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the alpha2- and beta3-adrenergic pathways. Pregnancy induces an intracytoplasmic modification of the lipolytic cascade, probably via hormone-sensitive lipase, with differences according to fat location.-Bousquet-Mélou, A., C. Muñoz, J. Galitzky, M. Berlan, and M. Lafontan. Pregnancy modifies the alpha2-beta-adrenergic receptor functional balance in rabbit fat cells.

  18. Beta-adrenergic receptors are differentially expressed in distinct interneuron subtypes in the rat hippocampus.

    Science.gov (United States)

    Cox, David J; Racca, Claudia; LeBeau, Fiona E N

    2008-08-20

    Noradrenaline (NA) acting via beta-adrenergic receptors (betaARs) plays an important role in the modulation of memory in the hippocampus. betaARs have been shown to be expressed in principal cells, but their distribution across different interneuron classes is unknown. We have used specific interneuron markers including calcium binding proteins (parvalbumin, calbindin, and calretinin) and neuropeptides (somatostatin, neuropeptide Y, and cholecystokinin) together with either beta1AR or beta2AR to determine the distribution of these receptors in all major subfields of the hippocampus. We found that beta1AR-expressing interneurons were more prevalent in the CA3 and CA1 regions of the hippocampus than in the dentate gyrus, where they were relatively sparse. beta2AR-expressing interneurons were more uniformly distributed between all three regions of the hippocampus. A high proportion of neuropeptide Y-containing interneurons in the dentate gyrus co-expressed beta2AR. beta1AR labeling was common in interneurons expressing somatostatin and parvalbumin in the CA3 and CA1 regions, particularly in the stratum oriens of these regions. beta2AR labeling was more likely to be found than beta1AR labeling in cholecystokinin-expressing interneurons. In contrast, calretinin-containing interneurons were virtually devoid of beta1AR or beta2AR labeling. These regional and interneuron type-specific differences suggest functionally distinct roles for NA in modulating hippocampal activity via activation of betaARs.

  19. Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke

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    Larue, D.; Kato, G.

    1981-04-09

    The concentration of alpha- and beta-adrenergic receptors--as measured by specific (/sup 3/H)WB-4101 and (-)-(/sup 3/H)dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for (/sup 3/H)WB-4101 was identical in exposed (KD . 0.34 +/- 0.09 nM) and control (KD . 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-(3H)dihydroalprenolol binding (exposed, KD . 2.83 +/- 0.30 mM vs. control KD . 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.

  20. The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms

    Directory of Open Access Journals (Sweden)

    Luong KV

    2012-12-01

    Full Text Available Khanh vinh quốc Lương, Lan Thi Hoàng NguyễnVietnamese American Medical Research Foundation, Westminster, California, USAAbstract: Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between β-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link β-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin–angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, β-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine β-adrenergic blockers as cancer therapeutics are required to further elucidate this role.Keywords: β-adrenergic blocker, neoplasm, β-adrenergic antagonism, non-genomic factor

  1. Pavlovian conditioning of morphine-induced alterations of immune status: evidence for peripheral beta-adrenergic receptor involvement.

    Science.gov (United States)

    Coussons-Read, M E; Dykstra, L A; Lysle, D T

    1994-09-01

    The present studies examined the involvement of peripheral beta-adrenergic receptor activity in the establishment and expression of conditioned morphine-induced alterations of immune status. Previous work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli which predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. During the training phase of these experiments, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, rats were reexposed to the conditioned stimulus prior to sacrifice. Saline or nadolol (0.002, 0.02, 0.2, or 2.0 mg/kg) was administered either prior to the training sessions or prior to the test session. Administration of nadolol prior to training did not affect the development of conditioned alterations of immune status. Conversely, nadolol administration prior to testing completely attenuated the expression of a subset of the conditioned morphine-induced changes in immune status. Taken together, these studies suggest that whereas peripheral beta-adrenergic receptor activity is not required for the establishment of conditioned morphine-induced alterations of immune status, it is involved in the expression of a subset of these conditioned immunomodulatory effects.

  2. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Doornbos, R.P.; Witkamp, R.F.; Greef, de J.; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (ß2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents

  3. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.; Doornbos, R.P.; Witkamp, R.F.; Greef, J. van der; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (beta2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agen

  4. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Doornbos, R.P.; Witkamp, R.F.; Greef, J. van der; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (β2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents

  5. Dynamin-association with agonist-mediated sequestration of beta-adrenergic receptor in single-cell eukaryote Paramecium.

    Science.gov (United States)

    Wiejak, Jolanta; Surmacz, Liliana; Wyroba, Elzbieta

    2004-04-01

    Evidence that dynamin is associated with the sequestration of the Paramecium beta(2)-adrenergic receptor (betaAR) immunoanalogue is presented. We previously reported a dramatic change in the distribution of betaAR analogue in the subcellular fractions upon isoproterenol treatment: it is redistributed from the membraneous to the cytosolic fraction, as revealed by quantitative image analysis of western blots. Here we confirm and extend this observation by laser scanning confocal and immunogold electron microscopy. In the presence of isoproterenol (10 micro mol l(-1)) betaAR translocated from the cell surface into dynamin-positive vesicles in the cytoplasmic compartment, as observed by dual fluorochrome immunolabeling in a series of the confocal optical sections. Colocalization of betaAR and dynamin in the tiny endocytic vesicles was detected by further electron microscopic studies. Generally receptor sequestration follows its desensitization, which is initiated by receptor phosphorylation by G-protein-coupled receptor kinase. We cloned and sequenced the gene fragment of 407 nucleotides homologous to the beta-adrenergic receptor kinase (betaARK): its deduced amino acid sequence shows 51.6% homology in 126 amino acids that overlap with the human betaARK2 (GRK3), and may participate in Paramecium betaAR desensitization. These results suggest that the molecular machinery for the desensitization/sequestration of the receptor immunorelated to vertebrate betaAR exists in unicellular PARAMECIUM:

  6. Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available Trace amine-associated receptors (TAAR are rhodopsin-like G-protein-coupled receptors (GPCR. TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR, phenylethylamine (PEA, octopamine (OA, but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1 and 2 (ADRB2 have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR octopamine (OAR, ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

  7. RT-PCR and Northern blot analysis in search for a putative Paramecium beta-adrenergic receptor.

    Science.gov (United States)

    Płatek, A; Wiejak, J; Wyroba, E

    1999-01-01

    RT-PCR and Northern blot analysis were performed in order to search for a putative beta-adrenergic receptor (beta-AR) in Paramecium using several beta2-adrenergic-specific molecular probes. Under strictly defined RT-PCR conditions DNA species of expected molecular size about 360 bp were generated with the primers corresponding to the universal mammalian beta2-AR sequence tagged sites (located within the 4th and the 6th transmembrane regions of the receptor). This RT-PCR product hybridized in Southern blot analysis with the oligonucleotide probe designed to the highly conservative beta2-AR region involved in G-proteins interaction and located within the amplified region. Northern hybridization was performed on Paramecium total RNA and mRNA with human beta2-AR cDNA and two oligonucleotide probes: the first included Phe 290 involved in agonist binding (Strader et al., 1995) and the second was the backward RT-PCR primer. All these probes revealed the presence of about 2 kb mRNA which is consistent with the size of beta2-AR transcripts found in higher eukaryotes.

  8. Indices of brain beta-adrenergic receptor signal transduction in the learned helplessness animal model of depression.

    Science.gov (United States)

    Gurguis, G N; Kramer, G; Petty, F

    1996-01-01

    Both stress response and antidepressant drug action may be mediated by beta-adrenergic receptors (beta AR). Since learned helplessness is a stress-induced animal model of depression, beta AR are relevant to investigate in this model. To date, studies have measured changes in total receptor density (RT), but have not examined more detailed aspects of signal transduction mechanisms such as coupling of the receptor to GS protein. We have investigated brain beta AR coupling in the frontal cortex, hippocampus and hypothalamus of rats exposed to inescapable shock and then tested for learned helplessness, and in both tested and naive controls using [125I]-iodocyanopindolol (ICYP) as the ligand. Both antagonist-saturation and agonist-displacement experiments were conducted, and the specificity for the beta AR was optimized by excluding ICYP binding to 5HT1B receptors. The percentage receptor density in the high-conformational state (%RH) and the ratio of agonist (isoproterenol) dissociation constant from the receptor in the low-/high-conformational states (KL/KH) were used as indices of coupling to GS protein. No significant differences were found between rats developing learned helplessness and non-helpless rats after inescapable stress in any parameter measured in any brain region. In the frontal cortex, exposure to inescapable shock induced beta AR uncoupling from GS protein as suggested by a low KL/KH ratio both in helpless and non-helpless rats but not in either control group. In the hypothalamus, there were trends for higher RL, RT and KL/KH ratio in helpless rats and stressed controls compared to naive controls. These findings suggest that beta AR binding parameters in frontal cortex, hippocampus or hypothalamus did not differentiate between helpless and non-helpless rats. Changes in beta AR coupling observed in these brain regions may reflect effects of stress, which appeared to be region-specific, rather than stress-induced behavioral depression.

  9. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.

    2003-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

  10. Central beta-adrenergic receptors play an important role in the enhancing effect of voluntary exercise on learning and memory in rat.

    Science.gov (United States)

    Ebrahimi, Shima; Rashidy-Pour, Ali; Vafaei, Abbas A; Akhavan, Maziar M

    2010-03-17

    The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. The aim of this study was to examine the role of the beta-adrenergic system in voluntary exercise-induced enhancement of learning and memory in rat. In order to block the beta-adrenergic receptors, the animals were received propranolol (a beta-blocker), or nadolol (a peripherally acting beta-blocker) before each night of five consecutive nights of exercise. Then their learning and memory were tested on the water maze task using a two-trials-per-day for 5 consecutive days. A probe trial was performed 2 days after the last training day. Our results showed that propranolol, but not nadolol reversed the exercise-induced improvement in learning and memory in rat. Our findings indicate that central beta-adrenergic receptors play an important role in mediating the beneficial effects of voluntary exercise on learning and memory.

  11. Activation of a GTP-binding protein and a GTP-binding-protein-coupled receptor kinase (beta-adrenergic-receptor kinase-1) by a muscarinic receptor m2 mutant lacking phosphorylation sites.

    Science.gov (United States)

    Kameyama, K; Haga, K; Haga, T; Moro, O; Sadée, W

    1994-12-01

    A mutant of the human muscarinic acetylcholine receptor m2 subtype (m2 receptor), lacking a large part of the third intracellular loop, was expressed and purified using the baculovirus/insect cell culture system. The mutant was not phosphorylated by beta-adrenergic-receptor kinase, as expected from the previous assignment of phosphorylation sites to the central part of the third intracellular loop. However, the m2 receptor mutant was capable of stimulating beta-adrenergic-receptor-kinase-1-mediated phosphorylation of a glutathione S-transferase fusion protein containing the m2 phosphorylation sites in an agonist-dependent manner. Both mutant and wild-type m2 receptors reconstituted with the guanine-nucleotide-binding regulatory proteins (G protein), G(o) and G(i)2, displayed guanine-nucleotide-sensitive high-affinity agonist binding, as assessed by displacement of [3H]quinuclidinyl-benzilate binding with carbamoylcholine, and both stimulated guanosine 5'-3-O-[35S]thiotriphosphate ([35S]GTP[S]) binding in the presence of carbamoylcholine and GDP. The Ki values of carbamoylcholine effects on [3H]quinuclidinyl-benzilate binding were indistinguishable for the mutant and wild-type m2 receptors. Moreover, the phosphorylation of the wild-type m2 receptor by beta-adrenergic-receptor kinase-1 did not affect m2 interaction with G proteins as assessed by the binding of [3H]quinuclidinyl benzilate or [35S]GTP[S]. These results indicate that (a) the m2 receptor serves both as an activator and as a substrate of beta-adrenergic-receptor kinase, and (b) a large part of the third intracellular loop of the m2 receptor does not contribute to interaction with G proteins and its phosphorylation by beta-adrenergic-receptor kinase does not uncouple the receptor and G proteins in reconstituted lipid vesicles.

  12. Ultrastructural characterization of noradrenergic- and beta-adrenergic receptor-containing profiles in the lateral nucleus of the amygdala

    Directory of Open Access Journals (Sweden)

    Claudia Farb

    2010-10-01

    Full Text Available Norepinephrine (NE is thought to play a key role in fear and anxiety, but its role in amygdala-dependent Pavlovian fear conditioning, a major model for understanding the neural basis of fear, is poorly understood. The lateral nucleus of the amygdala (LA is a critical brain region for fear learning and regulating the effects of stress on memory. To understand better the cellular mechanisms of NE and its adrenergic receptors in the LA, we used antibodies directed against dopamine beta-hydroxylase (DβH, the synthetic enzyme for NE, or against two different isoforms of the beta-adrenergic receptors (βARs, one that predominately recognizes neurons (βAR 248 and the other astrocytes (βAR 404, to characterize the microenvironments of DβH and βAR. By electron microscopy, most DβH terminals did not make synapses, but when they did, they formed both asymmetric and symmetric synapses. By light microscopy, βARs were present in both neurons and astrocytes. Confocal microscopy revealed that both excitatory and inhibitory neurons express βAR248. By electron microscopy, βAR 248 was present in neuronal cell bodies, dendritic shafts and spines, and some axon terminals and astrocytes. When in dendrites and spines, βAR 248 was frequently concentrated along plasma membranes and at post-synaptic densities of asymmetric (excitatory synapses. βAR 404 was expressed predominately in astrocytic cell bodies and processes. These astrocytic processes were frequently interposed between unlabeled terminals or ensheathed asymmetric synapses. Our findings provide a morphological basis for understanding ways in which NE may modulate transmission by acting via synaptic or non-synaptic mechanisms in the LA.

  13. Alterations in the oxygen deficit-oxygen debt relationships with beta-adrenergic receptor blockade in man.

    Science.gov (United States)

    Hughson, R L

    1984-04-01

    The effects of beta-adrenergic receptor blockade (100 mg oral metoprolol) or matched placebo on gas exchange kinetics were studied in six males. Ventilation and gas exchange were monitored in four transitions for each treatment from loadless pedalling (0 W) to a selected work rate (100 W) and back to 0 W. Breath-by-breath data were averaged for analysis. Oxygen uptake (VO2) kinetics were significantly slowed at the onset of exercise and recovery by beta-blockade. This resulted in larger oxygen deficit and oxygen debt (671 +/- 115, 586 +/- 87 ml O2, respectively) for beta-blockade than for placebo (497 +/- 87, 474 +/- 104 ml O2). In addition, oxygen deficit was significantly larger than oxygen debt during beta-blockade tests. These results can be explained by greater utilization of oxygen and creatine phosphate stores as well as anaerobic glycolysis at the onset of 100 W exercise with beta-blockade. Carbon dioxide output (VCO2) kinetics were significantly slowed by beta-blockade only at the onset of exercise. Expired ventilation (VE) kinetics were not affected by beta-blockade. At 0 W, VE was significantly reduced by beta-blockade. Heart rate was lower at all times with beta-blockade. Kinetics of heart rate were not affected. These data for VO2 kinetics at the start and end of exercise indicate that even in moderate-intensity exercise, lactic acid production can contribute significantly to energy supply. The use of the term ' alactic ' to describe the deficit and debt associated with this exercise is not appropriate.

  14. Simultaneous stimulation of GABA and beta adrenergic receptors stabilizes isotypes of activated adenylyl cyclase heterocomplex

    Directory of Open Access Journals (Sweden)

    Robichon Alain

    2004-06-01

    Full Text Available Abstract Background We investigated how the synthesis of cAMP, stimulated by isoproterenol acting through β-adrenoreceptors and Gs, is strongly amplified by simultaneous incubation with baclofen. Baclofen is an agonist of δ-aminobutyric acid type B receptors [GABAB], known to inhibit adenylyl cyclase via Gi. Because these agents have opposite effects on cAMP levels, the unexpected increase in cAMP synthesis when they are applied simultaneously has been intensively investigated. From previous reports, it appears that cyclase type II contributes most significantly to this phenomenon. Results We found that simultaneous application of isoproterenol and baclofen specifically influences the association/dissociation of molecules involved in the induction and termination of cyclase activity. Beta/gamma from [GABA]B receptor-coupled Gi has a higher affinity for adenylyl cyclase isoform(s when these isoforms are co-associated with Gs. Our data also suggest that, when beta/gamma and Gαs are associated with adenylyl cyclase isoform(s, beta/gamma from [GABA]B receptor-coupled Gi retards the GTPase activity of Gαs from adrenergic receptor. These reciprocal regulations of subunits of the adenylyl cyclase complex might be responsible for the drastic increase of cAMP synthesis in response to the simultaneous signals. Conclusions Simultaneous signals arriving at a particular synapse converge on molecular detectors of coincidence and trigger specific biochemical events. We hypothesize that this phenomenon comes from the complex molecular architectures involved, including scaffolding proteins that make reciprocal interactions between associated molecules possible. The biochemistry of simultaneous signaling is addressed as a key to synaptic function.

  15. Beta-Adrenergic Receptors and Mechanisms in Asthma: The New Long-Acting Beta-Agonists

    Directory of Open Access Journals (Sweden)

    Robert G Townley

    1996-01-01

    Full Text Available The objective is to review β-adrenergic receptors and mechanisms in the immediate and late bronchial reaction in asthma and the new long-acting β-agonist. This will be discussed in light of the controversy of the potential adverse effect of regular use of long-acting β-agonists. We studied the effect of formoterol on the late asthmatic response (LAR and airway inflammation in guinea-pigs. Formoterol suppressed the LAR, antigen-induced airway inflammation and hyperresponsiveness, although isoproterenol failed to inhibit these parameters. β-Adrenergic hyporesponsiveness, and cholinergic and a- adrenergic hyperresponsiveness have been implicated in the pathogenesis of asthma. A decrease in β-adrenoreceptor function can result either from exogenously administered β-agonist or from exposure to allergens resulting in a late bronchial reaction. There is increasing evidence that eosinophils, macrophages, and lymphocytes which are of primary importance in the late bronchial reaction are also modulated by β2- adrenoreceptors. In functional studies of guinea-pig or human isolated trachea and lung parenchyma, PAF and certain cytokines significantly reduced the potency of isoproterenol to reverse methacholine- or histamine-induced contraction. The effect of glucocorticoids on pulmonary β-adrenergic receptors and responses suggests an important role for glucocorticoids to increase β-adrenergic receptors and responsiveness.

  16. beta. -adrenergic receptor-mediated hepatic glycogenolysis is increased in aged male rats

    Energy Technology Data Exchange (ETDEWEB)

    Herring, P.A.; Graham, S.M.; Arinze, I.J.

    1986-03-05

    The effect of age on catecholamine-stimulated glycogenolysis was studied in isolated hepatocytes prepared from 3, 12, and 24 month-old rats. Glucose release was stimulated by epinephrine and norepinephrine, this was inhibited by phentolamine and prazosin. Isoproterenol (ISO) stimulated glycogenolysis only in cells from 24 month-old rats, this was blocked by propranolol. In liver plasma membranes, binding of (/sup 3/H)yohimbine (100-130 fmol/mg protein) did not change with age, whereas (/sup 3/H)prazosin binding decreased from 870 fmol/mg at 3 months to 435 fmol/mg at 12 months, but subsequently rose to 656 fmol/mg at 24 months. (/sup 125/I)Cyanopindolol binding increased from 8 fmol/mg at 3 months to 19 fmol/mg at 24 months. The proportion of ..beta..-receptors in the high affinity state increased from 28% at 3 months to 42% at 24 months. ISO stimulated adenylate cyclase at 24 months but not at 3 months. Basal, fluoride-, GTP-, and Gpp(NH)p-stimulated activities were 1.4- to 2.4-fold greater at 24 months than at 3 months. These results suggest an age-related increase in the sensitivity of adenylate cyclase to ..beta..-receptor stimulation.

  17. Fluorescence histochemical study of the localisation and distribution of beta-adrenergic receptor sites in the spinal cord and cerebellum of the chicken.

    Science.gov (United States)

    Bondok, A A; Botros, K G; el-Mohandes, E A

    1988-10-01

    The distribution of beta-adrenergic receptor sites has been studied in chicken spinal cord and cerebellum using a fluorescent analogue of propranolol, 9-amino-acridin-propranolol (9-AAP). In the cervical and lumbar regions of the spinal cord, beta-adrenoceptor sites were concentrated on cell bodies of alpha-motor neurons of the dorsolateral and ventrolateral nuclear groups of the ventral horn. In the thoracic region, they were present on cell bodies of the preganglionic sympathetic nucleus (dorsal commissural nucleus). In the dorsal horn, the receptor sites were present mainly on cell bodies of columna dorsalis magnocellularis. Sparse distribution of fluorescence was present in other regions of the gray matter. In the cerebellum, a dense distribution of beta-adrenergic receptor sites was observed on Purkinje cell bodies and their apical dendrites. Sparse distribution of receptor sites was present on fine ramifications of Purkinje cell dendrites in the molecular layer. Receptor sites were absent in the granule cell layer and the white matter. These observations indicate that alpha-motor neurons, preganglionic sympathetic neurons, neurons of columna dorsalis magnocellularis, and Purkinje cells are adrenoceptive, while granule cells are non-adrenoceptive.

  18. Beta-adrenergic receptor sensitivity, autonomic balance and serotonergic activity in practitioners of Transcendental Meditation

    Energy Technology Data Exchange (ETDEWEB)

    Hill, D.A.

    1989-01-01

    The aim of this thesis was to investigate the acute autonomic effects of the Transcendental Meditation Program (TM) and resolve the conflict arising from discrepant neurochemical and psychophysiological data. Three experimental investigations were performed. The first examined beta{sub 2}-adrenergic receptors (AR's) on peripheral blood lymphocytes, via (I{sup 125})iodocyanopindolol binding, in 10 male mediating and 10 age matched non-meditating control subjects, to test the hypothesis that the long-term practice of TM and the TM Sidhi Program (TMSP) reduces end organ sensitivity to adrenergic agonists. The second investigated respiratory sinus arrhythmia (an indirect measure of cardiac Parasympathetic Nervous System tone), and skin resistance (a measure of Sympathetic Nervous System tone) during periods of spontaneous respiratory apneusis, a phenomenon occurring during TM that is known to mark the subjective experience of transcending. The third was within subject investigation of the acute effects of the TMSP on 5-hydroxytryptamine (5-HT) activity. Platelet 5-HT was assayed by high pressure liquid chromatography with electrochemical detection, plasma prolactin (PL) and lutenizing hormone (LH) by radioimmunoassay, tryptophan by spectrofluorimetry, and alpha-1-acid glycoprotein (AGP, a modulator of 5-HT uptake) by radial immunodiffusion assay.

  19. Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts.

    Science.gov (United States)

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S

    2008-06-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP2 (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP2 receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function.

  20. Effect of. cap alpha. -,. beta. -adrenergic receptor agonists and antagonists of the efflux of /sup 22/Na and uptake of /sup 42/K by rat brain cortical slices

    Energy Technology Data Exchange (ETDEWEB)

    Phillis, J.W.; Wu, P.H.; Thierry, D.L.

    1982-03-18

    The effects of norepinephrine on ion fluxes in rat brain cortical slices have now been ascertained. /sup 22/Na efflux and /sup 42/K influx are enhanced by norepinephrine. The increase in ion fluxes can be blocked by ouabain, phentolamine and propranolol, suggesting that the catecholamine activates a membrane sodium pump by a receptor-mediated step. The facilitation of /sup 22/Na efflux is stereospecific as demonstrated by the very weak action of D-norepinephrine at 10/sup -5/ M concentration. Various ..cap alpha..-adrenergic and ..beta..-adrenergic receptor agonists, including oxymetazoline, naphazoline, clonidine, tramazoline, methoxamine, phenylephrine, L-isoproterenol and methoxyphenamine are potent stimulants of the sodium pump as demonstrated by their enhancement of ion fluxes in rat brain cortical slices. The results are consistent with the hypothesis that norepinephrine hyperpolarizes central neurons by activating an ouabain-sensitive, receptor-mediated sodium pump.

  1. Effect of Increased Cyclic AMP Concentration on Muscle Protein Synthesis and Beta-Adrenergic Receptor Expression in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, R. B.; Vaughn, J. R.; Bridge, K. Y.; Smith, C. K.

    1998-01-01

    Analogies of epinephrine are known to cause hypertrophy of skeletal muscle when fed to animals. These compounds presumably exert their physiological action through interaction with the P-adrenergic receptor. Since the intracellular signal generated by the Beta-adrenergic receptor is cyclic AMP (cAMP), experiments were initiated in cell culture to determine if artificial elevation of cAMP by treatment with forskolin would alter muscle protein metabolism and P-adrenergic receptor expression. Chicken skeletal muscle cells after 7 days in culture were treated with 0.2-30 micrometers forskolin for a total of three days. At the end of the treatment period, both the concentration of cAMP and the quantity of myosin heavy chain (MHC) were measured. Concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. In contrast, the quantity of MHC was increased approximately 50% above control cells at 0.2 micrometers forskolin, but exhibited a gradual decline at higher levels of forskolin so that the quantity of MHC in cells treated with 30 micrometers forskolin was not significantly different from controls. Curiously, the intracellular concentration of cAMP which elicited the maximum increase in the quantity of MHC was only 40% higher than cAMP concentration in control cells.

  2. The second Lilly Prize Lecture, University of Newcastle, July 1977. beta-Adrenergic receptor blockade in hypertension, past, present and future.

    Science.gov (United States)

    Prichard, B N

    1978-05-01

    All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III).

  3. Effect of Cardiopulmonary Bypass on Beta Adrenergic ReceptorAdenylate Cyclase System on Surfaces of Peripheral Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    LUO Ailin; TIAN Yuke; JIN Shiao

    2000-01-01

    The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP,IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after cardiopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces,which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.

  4. CRM 1-mediated degradation and agonist-induced down-regulation of beta-adrenergic receptor mRNAs.

    Science.gov (United States)

    Bai, Ying; Lu, Huafei; Machida, Curtis A

    2006-10-01

    The beta1-adrenergic receptor (beta1-AR) mRNAs are post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of its 3' untranslated region (UTR) with RNA binding proteins, including the HuR nuclear protein. In a previous report [Kirigiti et al. (2001). Mol. Pharmacol. 60:1308-1324], we examined the agonist-mediated down-regulation of the rat beta1-AR mRNAs, endogenously expressed in the rat C6 cell line and ectopically expressed in transfectant hamster DDT1MF2 and rat L6 cells. In this report, we determined that isoproterenol treatment of neonatal rat cortical neurons, an important cell type expressing beta1-ARs in the brain, results in significant decreases in beta1-AR mRNA stability, while treatment with leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in significant increases in beta1-AR mRNA stability and nuclear retention. UV-crosslinking/immunoprecipitation and glycerol gradient fractionation analyses indicate that the beta1-AR 3' UTR recognize complexes composed of HuR and multiple proteins, including CRM 1. Cell-permeable peptides containing the leucine-rich nuclear export signal (NES) were used as inhibitors of CRM 1-mediated nuclear export. When DDT1MF2 transfectants were treated with isoproterenol and peptide inhibitors, only the co-addition of the NES inhibitor reversed the isoproterenol-induced reduction of beta1-AR mRNA levels. Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the beta1-AR mRNAs.

  5. Acupuncture Attenuates Renal Sympathetic Activity and Blood Pressure via Beta-Adrenergic Receptors in Spontaneously Hypertensive Rats

    Science.gov (United States)

    Ye, Yang; Wang, Xue-Rui; Li, Fang; Xiao, Ling-Yong; Shi, Guang-Xia

    2017-01-01

    The sympathetic nervous system, via epinephrine and norepinephrine, regulates β-adrenergic receptor (β-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of β-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased β1-AR expression and improved β2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and β-ARs. PMID:28270938

  6. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    Directory of Open Access Journals (Sweden)

    Marion Emma André

    2015-05-01

    Full Text Available The noradrenergic (NA-system is an important regulator of cognitive function. It contributes to extinction learning(EL, and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR, regulates EL that depends on context, but is not fear-associated. We assessed behaviour in an ‘AAA’ or ‘ABA’ paradigm: rats were trained for 3 days in a T-maze(context-A to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL(unrewarded, whereby in the ABA-paradigm, EL was reinforced by a context change (B, and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded occurred. Typically, in control ‘AAA’ animals EL occurred on day 4 that progressed further on day 5. In control ‘ABA’ animals, EL also occurred on day 4, followed by renewal of the previously learned (A behavior on day 5, that was followed (in day 5 by extinction of this behavior, as the animals realised that no food reward would be given.Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the ‘ABA’ paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B. Furthermore, β-AR-antagonism prior to renewal testing (on day 5 in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the ‘A’ context.β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  7. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    Science.gov (United States)

    André, Marion Agnès Emma; Wolf, Oliver T.; Manahan-Vaughan, Denise

    2015-01-01

    The noradrenergic (NA)-system is an important regulator of cognitive function. It contributes to extinction learning (EL), and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR), regulates EL that depends on context, but is not fear-associated. We assessed behavior in an “AAA” or “ABA” paradigm: rats were trained for 3 days in a T-maze (context-A) to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL (unrewarded), whereby in the ABA-paradigm, EL was reinforced by a context change (B), and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded) occurred. Typically, in control “AAA” animals EL occurred on day 4 that progressed further on day 5. In control “ABA” animals, EL also occurred on day 4, followed by renewal of the previously learned (A) behavior on day 5, that was succeeded (on day 5) by extinction of this behavior, as the animals realised that no food reward would be given. Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the “ABA” paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B). Furthermore, β-AR-antagonism prior to renewal testing (on day 5) in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the “A” context. β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  8. beta-Adrenergic agonist activity of a monoclonal anti-idiotypic antibody.

    Science.gov (United States)

    Guillet, J G; Kaveri, S V; Durieu, O; Delavier, C; Hoebeke, J; Strosberg, A D

    1985-03-01

    Hybridoma cells bearing monoclonal antibody against the beta-adrenergic ligand alprenolol were used as an immunogen to raise monoclonal anti-idiotypic antibodies. Of six anti-idiotypic antibodies, which inhibit ligand binding, three were able to recognize beta-adrenergic receptors. One of them, mAb2B4, an IgM that could be amplified into ascites, binds to the beta-adrenergic catecholamine receptors of intact epidermoid A431 cells and precipitates receptors solubilized from plasma membranes by digitonin. This antibody identifies the beta 2-adrenergic receptor of A431 cells as a single 55-kDa protein and stimulates adenylate cyclase activity. This stimulation is inhibited by the beta-adrenergic antagonist propranolol.

  9. Development of a multiplex non-radioactive receptor assay : the benzodiazepine receptor, the serotonin transporter and the beta-adrenergic receptor

    NARCIS (Netherlands)

    de Jong, Lutea A. A.; Jeronimus-Stratingh, C. Margot; Cremers, Thomas I. F. H.

    2007-01-01

    Binding assays still form a fundamental part of modem drug development. Receptor binding assays are mostly based on radioactivity because of their speed, ease of use and reproducibility. Disadvantages, such as health hazards and production of radioactive waste, have prompted the development of non-r

  10. Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Ruderman, N B; Galbo, H

    1982-01-01

    The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min). Adrenergic stimulation...... was obtained by epinephrine in a physiological concentration (2.4 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively. Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers. In these fibers the effect...... of alpha-adrenergic receptors and had a positive inotropic effect during contractions which was abolished by alpha- as well as by beta-adrenergic blockade. The results indicate that epinephrine has profound effects on contracting muscle, and that these effects are elicited through different combinations...

  11. [Beta]-Adrenergic Receptor Activation Rescues Theta Frequency Stimulation-Induced LTP Deficits in Mice Expressing C-Terminally Truncated NMDA Receptor GluN2A Subunits

    Science.gov (United States)

    Moody, Teena D.; Watabe, Ayako M.; Indersmitten, Tim; Komiyama, Noboru H.; Grant, Seth G. N.; O'Dell, Thomas J.

    2011-01-01

    Through protein interactions mediated by their cytoplasmic C termini the GluN2A and GluN2B subunits of NMDA receptors (NMDARs) have a key role in the formation of NMDAR signaling complexes at excitatory synapses. Although these signaling complexes are thought to have a crucial role in NMDAR-dependent forms of synaptic plasticity such as long-term…

  12. Effects of thyroid hormone on. beta. -adrenergic responsiveness of aging cardiovascular systems

    Energy Technology Data Exchange (ETDEWEB)

    Tsujimoto, G.; Hashimoto, K.; Hoffman, B.B.

    1987-03-01

    The authors have compared the effects of ..beta..-adrenergic stimulation on the heart and peripheral vasculature of young (2-mo-old) and older (12-mo-old) rats both in the presence and absence of triiodothyronine (T/sub 3/)-induced hyperthyroidism. The hemodynamic consequences of T/sub 3/ treatment were less prominent in the aged hyperthyroid rats compared with young hyperthyroid rats (both in intact and pithed rats). There was a decrease in sensitivity of chronotropic responsiveness to isoproterenol in older pithed rats, which was apparently reversed by T/sub 3/ treatment. The number and affinity of myocardial ..beta..-adrenergic receptor sites measured by (/sup 125/I)cyanopindolol were not significantly different in young and older control rats; also, ..beta..-receptor density increased to a similar extent in both young and older T/sub 3/-treated rats. The ability of isoproterenol to relax mesenteric arterial rings, markedly blunted in older rats, was partially restored by T/sub 3/ treatment without their being any change in isoproterenol-mediated relaxation in the arterial preparation from young rats. The number and affinity of the ..beta..-adrenergic receptors measured in the mesenteric arteries was unaffected by either aging or T/sub 3/ treatment. The data suggest that effects of thyroid hormone and age-related alterations of cardiovascular responsiveness to ..beta..-adrenergic stimulation are interrelated in a complex fashion with a net result that the hyperkinetic cardiovascular manifestations in hyperthyroidism are attenuated in the older animals.

  13. Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

    Science.gov (United States)

    Sommer, Rebecca J; Hume, Adam J; Ciak, Jessica M; Vannostrand, John J; Friggens, Megan; Walker, Mary K

    2005-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.

  14. Dopaminergic and beta-adrenergic effects on gastric antral motility

    DEFF Research Database (Denmark)

    Bech, K; Hovendal, C P; Gottrup, F

    1984-01-01

    of bethanechol or pentagastrin inducing motor activity patterns as in the phase III of the MMC and the digestive state respectively. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by specifically acting dopaminergic blockers, while alpha- and beta......-adrenergic blockers were without any significant effects. Dose-response experiments with bethanechol and dopamine showed inhibition of a non-competitive type. Isoprenaline was used alone and in conjunction with selective blockade of beta 1- and beta 2-receptors during infusion of bethanechol which induces a pattern...... similar to phase III in the migrating myoelectric complex. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect could be significantly blocked by propranolol (beta 1 + beta 2-adrenoceptor blocker) and by using in conjunction the beta 1-adrenoceptor blocker practolol...

  15. Intracoronary genistein acutely increases coronary blood flow in anesthetized pigs through beta-adrenergic mediated nitric oxide release and estrogenic receptors.

    Science.gov (United States)

    Grossini, Elena; Molinari, Claudio; Mary, David A S G; Uberti, Francesca; Caimmi, Philippe Primo; Surico, Nicola; Vacca, Giovanni

    2008-05-01

    Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and alpha-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of beta(2)-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary N(omega)-nitro-L-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERalpha/ERbeta; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERalpha/ERbeta and the release of NO through vasodilatory beta(2)-adrenoreceptor effects.

  16. Synthesis and preliminary evaluation of aminoalkanol derivatives of selected azatricycloundecane system for binding with beta-adrenergic and 5HT1A and 5HT2A receptors.

    Science.gov (United States)

    Kossakowski, Jerzy; Kuran, Bozena

    2007-01-01

    A series of aminoalkanol derivatives of 8,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.0(2,6)] undec-8-en-1-yl acetate and 1,11-dimethyl-4-azatricyclo[5.2.2.0(2,6)]undecane-3,5,8-trione was prepared. The pharmacological profile of selected compounds was evaluated for affinity to beta-adrenoreceptors and serotoninergic receptors (5HT1A and 5HT2A).

  17. Cooperative regulation of non-small cell lung carcinoma by nicotinic and beta-adrenergic receptors: a novel target for intervention.

    Directory of Open Access Journals (Sweden)

    Hussein A N Al-Wadei

    Full Text Available Lung cancer is the leading cause of cancer death; 80-85% of lung cancer cases are non-small cell lung cancer (NSCLC. Smoking is a documented risk factor for the development of this cancer. Although nicotine does not have the ability to initiate carcinogenic events, recent studies have implicated nicotine in growth stimulation of NSCLC. Using three NSCLC cell lines (NCI-H322, NCI-H441 and NCI-H1299, we identified the cooperation of nicotinic acetylcholine receptors (nAChRs and β-adrenergic receptors (β-ARs as principal regulators of these effects. Proliferation was measured by thymidine incorporation and MTT assays, and Western blots were used to monitor the upregulation of the nAChRs and activation of signaling molecules. Noradrenaline and GABA were measured by immunoassays. Nicotine-treated NSCLC cells showed significant induction of the α7nAChR and α4nAChR, along with significant inductions of p-CREB and p-ERK1/2 accompanied by increases in the stress neurotransmitter noradrenaline, which in turn led to the observed increase in DNA synthesis and cell proliferation. Effects on cell proliferation and signaling proteins were reversed by the α7nAChR antagonist α-BTX or the β-blocker propranolol. Nicotine treatment also down-regulated expression of the GABA synthesizing enzyme GAD 65 and the level of endogenous GABA, while treatment of NSCLC cells with GABA inhibited cell proliferation. Interestingly, GABA acts by reducing β-adrenergic activated cAMP signaling. Our findings suggest that nicotine-induced activation of this autocrine noradrenaline-initiated signaling cascade and concomitant deficiency in inhibitory GABA, similar to modulation of these neurotransmitters in the nicotine-addicted brain, may contribute to the development of NSCLC in smokers. Our data suggest that exposure to nicotine either by tobacco smoke or nicotine supplements facilitates growth and progression of NSCLC and that pharmacological intervention by β blocker may

  18. The Relationship between Birthweight and Longitudinal Changes of Blood Pressure Is Modulated by Beta-Adrenergic Receptor Genes: The Bogalusa Heart Study

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2010-01-01

    Full Text Available This study examines the genetic influence of β-adrenergic receptor gene polymorphisms (β2-AR Arg16Gly and β3-AR Trp64Arg on the relationship of birthweight to longitudinal changes of blood pressure (BP from childhood to adulthood in 224 black and 515 white adults, aged 21–47 years, enrolled in the Bogalusa Heart Study. Blacks showed significantly lower birthweight and frequencies of β2-AR Gly16 and β3-AR Trp64 alleles and higher BP levels and age-related trends than whites. In multivariable regression analyses using race-adjusted BP and birthweight, low birthweight was associated with greater increase in age-related trend of systolic BP (standardized regression coefficient β=−0.09, P=.002 and diastolic BP (β=−0.07, P=.037 in the combined sample of blacks and whites, adjusting for the first BP measurement in childhood, sex, age, and gestational age. Adjustment for the current body mass index strengthened the birthweight-BP association. Importantly, the strength of the association, measured as regression coefficients, was modulated by the combination of β2-AR and β3-AR genotypes for systolic (P=.042 for interaction and diastolic BP age-related trend (P=.039 for interaction, with blacks and whites showing a similar trend in the interaction. These findings indicate that the intrauterine programming of BP regulation later in life depends on β-AR genotypes.

  19. Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle

    Science.gov (United States)

    Kirby, Christopher R.; Woodman, Christopher R.; Woolridge, Dale; Tischler, Marc E.

    1992-01-01

    Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

  20. Beta-adrenergic stimulation of phagocytosis in the unicellular eukaryote Paramecium aurelia.

    Science.gov (United States)

    Wyroba, E

    1989-08-01

    Bete-adrenergic agonists isoproterenol and norepinephrine enhanced phagocytosis in Paramecium. Stimulation was stereospecific, dose-dependent and inhibited by the beta-agonists propranolol and alprenolol. Phorbol ester and forskolin potentiated the stimulatory effect of catecholamines on Paramecium phagocytosis. The dansyl analogue of propranolol (DAPN) was used for fluorescent visualization of the beta-adrenergic receptor sites in Paramecium which have been found to be localized at the cell membrane and within the membrane of the nascent digestive vacuoles. The appearance of the characteristic fluorescent pattern has been blocked by 1-propranolol.

  1. The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man

    DEFF Research Database (Denmark)

    Philipsen, E K; Myhre, John Gabriel; Larsen, S;

    1990-01-01

    concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and beta......To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the agonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed...... hydroxybutyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man....

  2. Beta-adrenergic Blockade at Memory Encoding, but Not Retrieval, Decreases the Subjective Sense of Recollection.

    Science.gov (United States)

    Rimmele, Ulrike; Lackovic, Sandra F; Tobe, Russell H; Leventhal, Bennett L; Phelps, Elizabeth A

    2016-06-01

    Humans remember emotional events not only better but also exhibit a qualitatively distinct recollective experience-that is, emotion intensifies the subjective vividness of the memory, the sense of reliving the event, and confidence in the accuracy of the memory [Phelps, E. A., & Sharot, T. How (and why) emotion enhances the subjective sense of recollection. Current Directions in Psychological Science, 17, 147-152, 2008]. Although it has been demonstrated that activation of the beta-adrenergic system, linked to increases in stress hormone levels and physiological arousal, mediates enhanced emotional memory accuracy, the mechanism underlying the increased subjective sense of recollection is unknown. Behavioral evidence suggests that increased arousal associated with emotional events, either at encoding or retrieval, underlies their increased subjective sense of recollection. Using a double-blind, placebo-controlled, within-subject design, we showed that reducing arousal at encoding through oral intake of 80-mg of the beta-adrenergic receptor antagonist propranolol decreases the subjective sense of recollection for both negative and neutral stimuli 24 hr later. In contrast, administration of propranolol before memory retrieval did not alter the subjective sense of recollection. These results suggest that the neurohormonal changes underlying increased arousal at the time of memory formation, rather than the time of memory retrieval, modulate the subjective sense of recollection.

  3. Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

    Science.gov (United States)

    Ohyama, Katsuhiro; Inoue, Michiko

    2016-01-01

    Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

  4. PET measures of pre- and post-synaptic cardiac beta adrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Link, Jeanne M.; Stratton, John R.; Levy, Wayne; Poole, Jeanne E.; Shoner, Steven C.; Stuetzle, Werner; Caldwell, James H. E-mail: jcald@u.washington.edu

    2003-11-01

    Positron Emission Tomography was used to measure global and regional cardiac {beta}-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [{sup 11}C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [{sup 11}C]-CGP12177 was used to measure cell surface {beta}-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

  5. Phospholemman and beta-adrenergic stimulation in the heart.

    Science.gov (United States)

    Wang, JuFang; Gao, Erhe; Song, Jianliang; Zhang, Xue-Qian; Li, Jifen; Koch, Walter J; Tucker, Amy L; Philipson, Kenneth D; Chan, Tung O; Feldman, Arthur M; Cheung, Joseph Y

    2010-03-01

    Phosphorylation at serine 68 of phospholemman (PLM) in response to beta-adrenergic stimulation results in simultaneous inhibition of cardiac Na(+)/Ca(2+) exchanger NCX1 and relief of inhibition of Na(+)-K(+)-ATPase. The role of PLM in mediating beta-adrenergic effects on in vivo cardiac function was investigated with congenic PLM-knockout (KO) mice. Echocardiography showed similar ejection fraction between wild-type (WT) and PLM-KO hearts. Cardiac catheterization demonstrated higher baseline contractility (+dP/dt) but similar relaxation (-dP/dt) in PLM-KO mice. In response to isoproterenol (Iso), maximal +dP/dt was similar but maximal -dP/dt was reduced in PLM-KO mice. Dose-response curves to Iso (0.5-25 ng) for WT and PLM-KO hearts were superimposable. Maximal +dP/dt was reached 1-2 min after Iso addition and declined with time in WT but not PLM-KO hearts. In isolated myocytes paced at 2 Hz. contraction and intracellular Ca(2+) concentration ([Ca(2+)](i)) transient amplitudes and [Na(+)](i) reached maximum 2-4 min after Iso addition, followed by decline in WT but not PLM-KO myocytes. Reducing pacing frequency to 0.5 Hz resulted in much smaller increases in [Na(+)](i) and no decline in contraction and [Ca(2+)](i) transient amplitudes with time in Iso-stimulated WT and PLM-KO myocytes. Although baseline Na(+)-K(+)-ATPase current was 41% higher in PLM-KO myocytes because of increased alpha(1)- but not alpha(2)-subunit activity, resting [Na(+)](i) was similar between quiescent WT and PLM-KO myocytes. Iso increased alpha(1)-subunit current (I(alpha1)) by 73% in WT but had no effect in PLM-KO myocytes. Iso did not affect alpha(2)-subunit current (I(alpha2)) in WT and PLM-KO myocytes. In both WT and NCX1-KO hearts, PLM coimmunoprecipitated with Na(+)-K(+)-ATPase alpha(1)- and alpha(2)-subunits, indicating that association of PLM with Na(+)-K(+)-ATPase did not require NCX1. We conclude that under stressful conditions in which [Na(+)](i) was high, beta-adrenergic agonist

  6. Role of prostaglandin E2 in alterations of the beta-adrenergic system from rat eclamptic uterus.

    Science.gov (United States)

    Sales, M E; Borda, E S; Sterin-Borda, L; Arregger, A; Andrada, E C

    1995-09-28

    The inotropic effect of isoproterenol, as well as the beta-adrenoceptor population, was measured in pregnant uterine tissue from female spontaneous hypertensive rats (SHR) (control group: C) and female SHR that were grafted with skin from Holtzman male rats (eclamptic group: E). The Kd value of the concentration-response curve of isoproterenol was higher for uteri from E rats than C rats. This phenomenon was not accompanied by a modification in the expression of beta-adrenoceptors. Inhibition of the synthesis of prostaglandins prevented the hyporeactivity to isoproterenol during eclampsia. Moreover, uteri from E rats generated and released greater amounts of prostaglandin E2 (PGE2) than uteri from C rats, even in the presence or absence of isoproterenol. In addition, whereas isoproterenol administered alone increased basal cyclic AMP (cAMP) production from C uteri, PGE2 administered alone enhanced cAMP production in E uterine tissue. These results suggest that the decrease in beta-adrenergic response to the agonist in E rats is ascribed to PGE2 production. The abnormal reactivity to the beta-agonist could be associated with a heterologous desensitization of uterine beta-adrenoceptors exerted by PGE2 overload in uteri from E rats. These results bear directly on the regulation of uterine motility during pregnancy, since an impaired response to beta-adrenergic innervation could lead to increased uterine motility, impairing the maintenance of pregnancy.

  7. The rush to adrenaline: drugs in sport acting on the beta-adrenergic system.

    Science.gov (United States)

    Davis, E; Loiacono, R; Summers, R J

    2008-06-01

    Athletes attempt to improve performance with drugs that act on the beta-adrenergic system directly or indirectly. Of three beta-adrenoceptor (AR) subtypes, the beta(2)-AR is the main target in sport; they have bronchodilator and anabolic actions and enhance anti-inflammatory actions of corticosteroids. Although demonstrable in animal experiments and humans, there is little evidence that these properties can significantly improve performance in trained athletes. Their actions may also be compromised by receptor desensitization and by common, naturally occurring receptor mutations (polymorphisms) that can influence receptor signalling and desensitization properties in individuals. Indirectly acting agents affect release and reuptake of noradrenaline and adrenaline, thereby influencing all AR subtypes including the three beta-ARs. These agents can have potent psychostimulant effects that provide an illusion of better performance that does not usually translate into improvement in practice. Amphetamines and cocaine also have considerable potential for cardiac damage. beta-AR antagonists (beta-blockers) are used in sports that require steadiness and accuracy, such as archery and shooting, where their ability to reduce heart rate and muscle tremor may improve performance. They have a deleterious effect in endurance sports because they reduce physical performance and maximum exercise load. Recent studies have identified that many beta-AR antagonists not only block the actions of agonists but also activate other (mitogen-activated PK) signalling pathways influencing cell growth and fate. The concept that many compounds previously regarded as 'blockers' may express their own spectrum of pharmacological properties has potentially far-reaching consequences for the use of drugs both therapeutically and illicitly.

  8. DNA synthesis in mouse brown adipose tissue is under. beta. -adrenergic control

    Energy Technology Data Exchange (ETDEWEB)

    Rehnmark, S.; Nedergaard, J. (Univ. of Stockholm (Sweden))

    1989-02-01

    The rate of DNA synthesis in mouse brown adipose tissue was followed with injections of ({sup 3}H)thymidine. Cold exposure led to a large increase in the rate of ({sup 3}H)thymidine incorporation, reaching a maximum after 8 days, after which the activity abruptly ceased. A series of norepinephrine injections was in itself able to increase ({sup 3}H)thymidine incorporation. When norepinephrine was injected in combination with the {alpha}-adrenergic antagonist phentolamine or with the {beta}-adrenergic antagonist propranolol, the stimulation was fully blocked by propranolol. It is suggested that stimulation of DNA synthesis in brown adipose tissue is a {beta}-adrenergically mediated process and that the tissue is an interesting model for studies of physiological control of DNA synthesis.

  9. [Sleep disturbances in Smith-Magenis syndrome: treatment with melatonin and beta-adrenergic antagonists].

    Science.gov (United States)

    Van Thillo, A; Devriendt, K; Willekens, D

    2010-01-01

    Smith-Magenis syndrome is a generic disorder, characterised by physical, neurological and behavioural features and caused by a 17p11.2 deletion. Patients with this syndrome typically display an inversion of the sleep-wake cycle. In this article we describe clinical developments in a two-year-old girl with Smith-Magenis syndrome whose sleep problems were successfully treated with melatonin and beta-adrenergic blockers. We also mention relevant data obtained in our literature search.

  10. Beta-Adrenergic gene therapy for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Koch Walter J

    2000-10-01

    Full Text Available Abstract Gene therapy using in vivo recombinant adenovirus-mediated gene transfer is an effective technique that offers great potential to improve existing drug treatments for the complex cardiovascular diseases of heart failure and vascular smooth muscle intimal hyperplasia. Cardiac-specific adenovirus-mediated transfer of the carboxyl-terminus of the β-adrenergic receptor kinase (βARKct, acting as a Gβγ-β-adrenergic receptor kinase (βARK1 inhibitor, improves basal and agonist-induced cardiac performance in both normal and failing rabbit hearts. In addition, βARKct adenovirus infection of vascular smooth muscle is capable of significantly diminishing neointimal proliferation after angioplasty. Therefore, further investigation is warranted to determine whether inhibition of βARK1 activity and sequestration of Gβγ via an adenovirus that encodes the βARKct transgene might be a useful clinical tool for the treatment of cardiovascular pathologies.

  11. Effect of beta-ADrenergic Agonist on Cyclic AMP Synthesis in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Because it seems logical that these agonists exert their action on muscle through stimulation of cAMP synthesis, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate cAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of cAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of cAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax levels were approximately 15-fold weaker than isoproterenol in stimulating the rate of cAMP synthesis. In addition, the EC50 values for isoproterenol, cimaterol, clenbuterol, epinephrine, and albuterol were 360 nM, 630 nM, 900 nM, 2,470 nM, and 3,650 nM, respectively. Finally, dose response curves show that the concentrations of cimaterol and clenbuterol in culture media at concentrations known to cause significant muscle hypertrophy in animals had no detectable effect on stimulation of CAMP accumulation in chicken skeletal muscle cells.

  12. Beta-adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling.

    Science.gov (United States)

    Watt, Matthew J; Steinberg, Gregory R; Chan, Stanley; Garnham, Andrew; Kemp, Bruce E; Febbraio, Mark A

    2004-09-01

    Hormone-sensitive lipase (HSL), an important regulatory enzyme for triacylglycerol hydrolysis within skeletal muscle, is controlled by beta-adrenergic signaling as well as intrinsic factors related to contraction and energy turnover. In the current study, we tested the capacity of 5'AMP-activated protein kinase (AMPK) to suppress beta-adrenergic stimulation of HSL activity. Eight male subjects completed 60 min of cycle exercise at 70% VO2 peak on two occasions: either with normal (CON) or low (LG) pre-exercise muscle glycogen content, which is known to enhance exercise-induced AMPK activity. Muscle samples were obtained before and immediately after exercise. Pre-exercise glycogen averaged 375 +/- 35 and 163 +/- 27 mmol x kg(-1) dm for CON and LG, respectively. AMPK alpha-2 was not different between trials at rest and was increased (3.7-fold, PHSL activity did not differ between trials at rest and increased (0 min: 1.67 +/- 0.13; 60 min: 2.60 +/- 0.26 mmol x min(-1) x kg(-1) dm) in CON. The exercise-induced increase in HSL activity was attenuated by AMPK alpha-2 activation in LG. The attenuated HSL activity during LG occurred despite higher plasma epinephrine levels (60 min: CON, 1.96 +/- 0.29 vs LG, 4.25 +/- 0.60 nM, PHSL activity in LG, IMTG was decreased by exercise (0 min: 27.1 +/- 2.0; 60 min: 22.5 +/- 2.0 mmol x kg(-1) dm, PHSL activity, we performed experiments in muscle cell culture. The epineprine-induced increase in HSL activity was totally attenuated (PHSL activity that can override beta-adrenergic stimulation. However, the increased IMTG degradation in LG suggests factors other than HSL activity are important for IMTG degradation.

  13. Antidiuretic effect of ritodrine with and without beta-adrenergic blockade.

    Science.gov (United States)

    Gerritse, R; Pinas, I M; Reuwer, P J; Haspels, A A; Charbon, G A; Beijer, H J

    1985-11-01

    Dose-related effects of ritodrine and ritodrine combined with metoprolol on urinary excretion rate were studied in anesthetized dogs. Urine production was abruptly reduced after a total dose of 4 micrograms.kg-1 of ritodrine. This effect could not be antagonized by metoprolol, although the ritodrine-induced decrease of mean arterial pressure and renal arterial blood flow was significantly inhibited. The possible role of fluid retention during tocolytic treatment, even with beta-adrenergic blockade, in the etiology of pulmonary edema is discussed with a review on recent literature.

  14. Beta-adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats.

    Science.gov (United States)

    Frank, J A; Wang, Y; Osorio, O; Matthay, M A

    2000-10-01

    To determine whether beta-adrenergic agonist therapy increases alveolar liquid clearance during the resolution phase of hydrostatic pulmonary edema, we studied alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left atrial pressure to 25 cmH(2)O and instilling 6 ml/kg body wt isotonic 5% albumin (prepared from bovine albumin) in normal saline into the distal air spaces of each lung. After 1 h, sheep were treated with a nebulized beta-agonist (salmeterol) or nebulized saline (controls), and left atrial pressure was then returned to normal. beta-Agonist therapy resulted in a 60% increase in alveolar liquid clearance over 3 h (P Ringer lactate). beta-Agonist therapy resulted in a significant decrease in excess lung water (P < 0.01) and significant improvement in arterial blood gases by 2 h (P < 0.03). These preclinical experimental studies support the need for controlled clinical trials to determine whether beta-adrenergic agonist therapy would be of value in accelerating the resolution of hydrostatic pulmonary edema in patients.

  15. Effect of beta-adrenergic stimulants on cytotoxicity of mitomycin C in HeLa cells.

    Science.gov (United States)

    Miyamoto, K; Sanae, F; Iwasaki, M; Koshiura, R

    1982-12-01

    Effects of several autonomic agents on the cytotoxicity of mitomycin C in HeLa cells were studied. When beta-adrenergic stimulants such as isoproterenol, epinephrine, terbutaline and turobuterol were added at concentrations over 10(-14) M 15 to 60 min before mitomycin C, the colony-forming ability of HeLa cells was significantly inhibited more than by mitomycin C alone. The action of isoproterenol and epinephrine on the colony-forming ability of the cells was abolished by propranolol. The intracellular cyclic AMP level of HeLa cells reached the peak of about two-fold the basal level at 30 min after the addition of 10(-8) M isoproterenol. In combination with mitomycin C, the high level of intracellular cyclic AMP induced by isoproterenol was maintained for a significantly longer period in comparison with that by isoproterenol alone, while mitomycin C alone caused essentially no change in the cyclic AMP level. The pretreatment with dibutyryl cyclic AMP also enhanced the effect of mitomycin C. From these findings, it is strongly suggested that the synergistic effect of beta-adrenergic stimulants on the cytotoxicity of mitomycin C is mediated via stimulation of the beta-adrenoceptors of HeLa cells which elevates the intracellular cyclic AMP for a long time in combination with mitomycin C.

  16. Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery.

    Directory of Open Access Journals (Sweden)

    Hyoung Kyu Kim

    Full Text Available BACKGROUND AND PURPOSE: Beta adrenergic overstimulation may increase the vascular damage and stroke. However, the underlying mechanisms of beta adrenergic overstimulation in cerebrovascular dysfunctions are not well known. We investigated the possible cerebrovascular dysfunction response to isoproterenol induced beta-adrenergic overstimulation (ISO in rabbit cerebral arteries (CAs. METHODS: ISO was induced in six weeks aged male New Zealand white rabbit (0.8-1.0 kg by 7-days isoproterenol injection (300 μg/kg/day. We investigated the alteration of protein expression in ISO treated CAs using 2DE proteomics and western blot analysis. Systemic properties of 2DE proteomics result were analyzed using bioinformatics software. ROS generation and following DNA damage were assessed to evaluate deteriorative effect of ISO on CAs. Intracellular Ca(2+ level change and vascular contractile response to vasoactive drug, angiotensin II (Ang II, were assessed to evaluate functional alteration of ISO treated CAs. Ang II-induced ROS generation was assessed to evaluated involvement of ROS generation in CA contractility. RESULTS: Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1 in ISO-CAs. As a cause of dysregulation of actin-cytoskeleton organization, we found decreased level of RhoA and ROCK1, which are major regulators of actin-cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca(2+ efflux and constriction response to angiotensin II and high K(+ in ISO-CAs. ISO also increased basal ROS generation and induced oxidative damage in CA; however, it decreased the Ang II-induced ROS generation rate. These results indicate that ISO disrupted actin cytoskeleton proteome network

  17. Participation of beta-adrenergic activity in modulation of GLUT4 expression during fasting and refeeding in rats

    Science.gov (United States)

    Through in vitro studies, several factors have been reported as modulators of GLUT4 gene expression. However, the role(s) of each potential GLUT4 modulator is not completely understood in the in vivo setting. The present study has investigated the hypothesis that beta-adrenergic stimulation particip...

  18. Sympathetic nerve activity in normal and cystic follicles from isolated bovine ovary: local effect of beta-adrenergic stimulation on steroid secretion

    Directory of Open Access Journals (Sweden)

    Ortega Hugo H

    2011-05-01

    Full Text Available Abstract Cystic ovarian disease (COD is an important cause of abnormal estrous behavior and infertility in dairy cows. COD is mainly observed in high-yielding dairy cows during the first months post-partum, a period of high stress. We have previously reported that, in lower mammals, stress induces a cystic condition similar to the polycystic ovary syndrome in humans and that stress is a definitive component in the human pathology. To know if COD in cows is also associated with high sympathetic activity, we studied isolated small antral (5mm, preovulatory (10mm and cystic follicles (25mm. Cystic follicles which present an area 600 fold greater compared with preovulatory follicles has only 10 times less concentration of NE as compared with small antral and preovulatory follicles but they had 10 times more NE in follicular fluid, suggesting a high efflux of neurotransmitter from the cyst wall. This suggestion was reinforced by the high basal release of recently taken-up 3H-NE found in cystic follicles. While lower levels of beta-adrenergic receptor were found in cystic follicles, there was a heightened response to the beta-adrenergic agonist isoproterenol and to hCG, as measured by testosterone secretion. There was however an unexpected capacity of the ovary in vitro to produce cortisol and to secrete it in response to hCG but not to isoproterenol. These data suggest that, during COD, the bovine ovary is under high sympathetic nerve activity that in addition to an increased response to hCG in cortisol secretion could participate in COD development.

  19. A case of life-threatening lactic acidosis after smoke inhalation - interference between beta-adrenergic agents and ethanol?

    Science.gov (United States)

    Taboulet, P; Clemessy, J L; Freminet, A; Baud, F J

    1995-12-01

    A 49-year-old male developed bronchospasm and severe lactic acidosis after exposition to fire smoke. The correction of lactic acidosis following beta-adrenergic agents withdrawal, and the transitory increase in lactate after salbutamol reintroduction are consistent with hypersensitivity to salbutamol. However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h after admission is far above those currently seen after administration of beta-adrenergic agents. We searched for causes able to potentiate the adverse effects of these drugs and we noticed that our patient had a high plasma ethanol level (2.4 g/l). Alcohol metabolism in the liver results in generation of high NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation suggests that plasma lactate levels should be monitored closely in alcoholic patients treated with beta-mimetic agents.

  20. Glucose-induced thermogenesis in patients with small cell lung carcinoma. The effect of acute beta-adrenergic inhibition

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Tuxen, C

    1994-01-01

    Seven patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g on two occasions to examine the effect of glucose on whole body and forearm thermogenesis with and without acute beta-adrenergic inhibition with propranolol. Whole body energy expenditure...... was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. The uptake of oxygen in the forearm was calculated as the product of the forearm blood flow and the difference in arteriovenous oxygen concentration. The glucose......-induced forearm oxygen uptake in the period 60-120 min following the glucose load was significantly reduced after beta-adrenergic inhibition from 103 +/- 28 mumol 100 g-1 60 min-1 to 29 +/- 29 mumol 100 g-1 60 min-1 (P blood was not increased...

  1. Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Greeley, G.H. Jr.; Lluis, F.; Gomex, G.; Ishizuka, J.; Holland, B.; Thompson, J.C. (Univ. of Texas Medical Branch, Galveston (USA))

    1988-04-01

    Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids that share structural homologies with pancreatic polypeptide (PP). PP is predominantly found in the endocrine pancreas. PYY is primarily found in mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY is found in both the peripheral and central nervous system. Previous studies indicate that these peptides can interact with the autonomic nervous system. The objective of the present experiments was to study the effect of PYY on neurally stimulated insulin release in conscious dogs. Intravenous administration of PYY (100, 200, and 400 pmol{center dot}kg{sup {minus}1} {center dot}h{sup {minus}1}) reduced 2-DG-stimulated insulin release in a dose-dependent manner (P <0.05) without affecting plasma glucose levels. Administration of NPY, but not PP, reduced 2-DG-stimulated release of insulin. The inhibitory action of PYY on 2-DG-stimulated insulin release persisted in the presence of atropine or phentolamine treatment; however, hexamethonium alone or phentolamine plus propranolol treatment blocked the inhibitory action of PYY. Release of insulin stimulated by the {beta}-agonist isoproterenol was also inhibited by PYY. These results indicate that PYY can inhibit autonomic neurotransmission by a mechanism that may involve ganglionic or postganglionic inhibition of {beta}-adrenergic stimulation. The findings suggest a role for PYY and NPY in the autonomic regulation of insulin release.

  2. A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.

    Science.gov (United States)

    Marion-Latard, F; De Glisezinski, I; Crampes, F; Berlan, M; Galitzky, J; Suljkovicova, H; Riviere, D; Stich, V

    2001-01-01

    This study was designed to assess whether physiological activation of the sympathetic nervous system induced by exercise changes adipose tissue responsiveness to catecholamines in humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men (age: 22. 3 +/- 1.5 yr; body mass index: 23.0 +/- 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (beta(1)-agonist), or terbutaline (beta(2)-agonist) perfused during 30 min through probes before and after 60-min exercise (50% of the maximal aerobic power). The increase in extracellular glycerol concentration during infusion was significantly lower after the exercise when compared with the increase observed before the exercise (P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in norepinephrine-induced glycerol increase between the two infusions was observed. To assess the involvement of catecholamines in the blunted beta-adrenergic-induced lipolytic response after exercise, adipose tissue adrenergic sensitivity was explored with two 60-min infusions of norepinephrine or epinephrine separated by a 60-min interval. With both catecholamines, the increase in glycerol was significantly lower during the second infusion (P < 0.05). The findings suggest that aerobic exercise, which increased adrenergic activity, induces a desensitization in beta(1)- and beta(2)-adrenergic lipolytic pathways in human subcutaneous adipose tissue.

  3. G-Protein Inwardly Rectifying Potassium Channel 1 (GIRK1 Knockdown Decreases Beta-Adrenergic, MAP Kinase and Akt Signaling in the MDA-MB-453 Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Michael W. Hance

    2008-01-01

    Full Text Available Previous data from our laboratory have indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1 in breast cancer cell lines and that these pathways are involved in growth regulation of these cells. To determine functionality, MDA-MB-453 breast cancer cells were stimulated with ethanol, known to open GIRK channels. Decreased GIRK1 protein levels were seen after treatment with 0.12% ethanol. In addition, serum-free media completely inhibited GIRK1 protein expression. This data indicates that there are functional GIRK channels in breast cancer cells and that these channels are involved in cellular signaling. In the present research, to further define the signaling pathways involved, we performed RNA interference (siRNA studies. Three stealth siRNA constructs were made starting at bases 1104, 1315, and 1490 of the GIRK1 sequence. These constructs were transfected into MDA-MB-453 cells, and both RNA and protein were isolated. GIRK1, β2-adrenergic and 18S control levels were determined using real-time PCR 24 hours after transfection. All three constructs decreased GIRK1 mRNA levels. However, β2 mRNA levels were unchanged by the GIRK1 knockdown. GIRK1 protein levels were also reduced by the knockdown, and this knockdown led to decreases in beta-adrenergic, MAP kinase and Akt signaling.

  4. Beta-adrenergic modulation of tremor and corticomuscular coherence in humans.

    Directory of Open Access Journals (Sweden)

    Mark R Baker

    Full Text Available Coherence between the bioelectric activity of sensorimotor cortex and contralateral muscles can be observed around 20 Hz. By contrast, physiological tremor has a dominant frequency around 10 Hz. Although tremor has multiple sources, it is partly central in origin, reflecting a component of motoneuron discharge at this frequency. The motoneuron response to ~20 Hz descending input could be altered by non-linear interactions with ~10 Hz motoneuron firing. We investigated this further in eight healthy human subjects by testing the effects of the beta-adrenergic agents propranolol (non-selective β-antagonist and salbutamol (β(2-agonist, which are known to alter the size of physiological tremor. Corticomuscular coherence was assessed during an auxotonic precision grip task; tremor was quantified using accelerometry during index finger extension. Experiments with propranolol used a double-blind, placebo-controlled crossover design. A single oral dose of propranolol (40 mg significantly increased beta band (15.3-32.2 Hz corticomuscular coherence compared with placebo, but reduced tremor in the 6.2-11.9 Hz range. Salbutamol (2.5 mg was administered by inhalation. Whilst salbutamol significantly increased tremor amplitude as expected, it did not change corticomuscular coherence. The opposite direction of the effects of propranolol on corticomuscular coherence and tremor, and the fact that salbutamol enhances tremor but does not affect coherence, implies that the magnitude of corticomuscular coherence is little influenced by non-linear interactions with 10 Hz oscillations in motoneurons or the periphery. Instead, we suggest that propranolol and salbutamol may affect both tremor and corticomuscular coherence partly via a central site of action.

  5. Human adipose tissue blood flow during prolonged exercise, III. Effect of beta-adrenergic blockade, nicotinic acid and glucose infusion

    DEFF Research Database (Denmark)

    Bülow, J

    1981-01-01

    acid, during acute i.v. beta-adrenergic blockade by propranolol, and during continuous i.v. infusion of glucose. The most pronounced lipid mobilization and utilization during work was seen in the control experiments where ATBF rose 3-fold on average from the initial rest period to the third hour...... of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did...

  6. Metabolic consequences of beta-adrenergic receptor blockade for the acutely ischemic dog myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Westera, G.; Hollander, W. den; Wall, E.E. van der; Eenige, M.J. van; Scholtalbers, S.; Visser, F.C.; Roos, J.P.

    1984-02-01

    In an experimental study in 50 dogs the myocardial uptake of free fatty acids (FFAs) after beta-blockade was determined using radioiodinated heptadecanoic acid as a metabolic tracer. All 4 beta-blockers used (metoprolol, timolol, propranolol and pindolol) lowered the uptake of FFAs in the normal canine heart. Uptake of FFAs was also diminished after coronary artery occlusion per se, but administration of beta-blockers exerted little additional influence on the uptake of FFAs. This observation was qualitatively parallelled by the uptake of /sup 201/Tl in concomitant experiments. Plasma FFA levels were increased by pindolol (non-selective with intrinsic sympathomimetic activity), not changed by metoprolol (a cardioselective betablocking agent) and lowered by timolol and propranolol (both non-selective compounds). The extent of ischemic tissue, as reflected by uptake of iodoheptadecanoic acid and /sup 201/Tl, was diminished by metoprolol but not by other beta-blockers. Regional distribution of both tracers, as shown in the endo-epicardial uptake ratios, was hardly influenced by beta-blockade, except for a small increase of /sup 201/Tl uptake in non-occluded endocardium. Uptake of /sup 201/Tl as well as of iodoheptadecanoic acid in the ischemic area was increased by metoprolol, timolol and propranolol and decreased by pindolol. We conclude that beta-blocking agents confer different effects on myocardial uptake and metabolism of FFAs which might possibly be related to their different inherent properties.

  7. [Central effects of five beta-adrenergic receptor blockers in healthy volunteers: a quantitative EEG study].

    Science.gov (United States)

    Sabot, C; Pechadre, J C; Beudin, P; Lauxerois, M; Trolese, J F; Kantelip, J P; Ducher, J L; Gibert, J

    1989-03-01

    The effects of five beta blockers on the central nervous system of healthy subjects was studied by computerized EEG analysis. All subjects underwent continuous recording with a Holter magnetic type recorder during the experimental period. For 10 consecutive days, five groups of subjects received alternately placebo and the beta blockers acebutolol 600 mg, carteolol 20 mg, metoprolol 200 mg, pindolol 30 mg and sotalol 320 mg. EEG recordings (C4/P4, P4/02 and C3/P3, P3/01) lasting 5 min were made between 8.30 and 9.30 a.m. Subjects were at rest with eyes closed and there was no vigilance control. The signal was recorded on a magnetic tape recorder and then processed by Nicolet MED 80 system. Comparisons of absolute and relative powers and of average frequencies were then made between the different sequences and groups. The possible correlations between the changes observed in the power spectrum and the clinical, pharmacological and pharmacokinetic specific properties of each beta blocker are discussed.

  8. Lack of beta-adrenergic role for catecholamines in the development of hyperglycemia and ketonaemia following acute insulin withdrawal in type I diabetic patients.

    Science.gov (United States)

    Beylot, M; Sautot, G; Dechaud, H; Cohen, R; Riou, J P; Serusclat, P; Mornex, R

    1985-04-01

    In order to evaluate the role of beta-receptor mediated effects of catecholamines in the metabolic deterioration following insulin withdrawal in insulin-dependent diabetic patients we have measured in 5 patients metabolic substrate and hormone concentrations during a 6 hours arrest of insulin infusion, without or with a simultaneous infusion of propranolol. During insulin deprivation plasma epinephrine and norepinephrine increased slightly (from 107 +/- 10 ng/L to 173 +/- 6 ng/L and from 307 +/- 37 ng/L to 518 +/- 77/ng/L respectively (p less than 0.05), cortisol decreased physiologically, but growth hormone and glucagon were not significantly modified. Free insulin decreased progressively from 12.2 +/- 2.5 mU/L to 5.4 +/- 1.1 mU/L (p less than 0.01). Blood glucose and ketone bodies rose sharply before any significant change in catecholamine levels. Plasma free fatty acids and blood glycerol increased progressively and their rise appeared somewhat temporally related to the variations of catecholamine levels. The addition of propranolol to insulin deprivation did not modify the changes in hormone concentrations in spite of a slightly greater rise of epinephrine (from 78 +/- 4 ng/L to 179 +/- 7 ng/L, p less than 0.05) and norepinephrine (from 395 +/- 80 ng/L to 679 +/- 153 ng/L, p less than 0.05). The rises of glucose and ketone bodies were unaffected whereas the increases of free fatty acids and glycerol were slightly blunted. In conclusion, we have no evidence for a beta-adrenergic mediated role for catecholamines in the development of hyperglycaemia and ketonaemia in non-stressed insulin deprived diabetic patients, and only small evidence for a permissive effect on lipolysis.

  9. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Bendtsen, F; Henriksen, Jens Henrik Sahl

    2001-01-01

    with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. METHODS: Twenty patients with cirrhosis underwent a haemodynamic......) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P beta-adrenergic blockade (1.27 versus 1.29 ml/mmHg, +2%, ns), whereas...... with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis....

  10. Exercise performance and beta-adrenergic blockade in patients with complete heart block treated with ventricular inhibited pacing.

    Science.gov (United States)

    Wikner, J; Larsen, F F; Nordlander, R; Pehrsson, K; Aström, H

    1991-09-01

    The effect of beta-adrenergic blockade (propranolol) on exercise performance was studied in 15 patients (12 men and 3 women, mean age 70 years) with complete heart block treated with a ventricular-inhibited pacemaker (VVI). In a double-blind procedure, the patients were randomly given either 0.1 mg/kg of propranolol or saline solution i.v. before a first exercise test and vice versa before a second test. The interval between the tests was 24 hours. Nine patients were in sinus rhythm, 4 patients had atrial flutter, and 2 others had atrial fibrillation. The exercise capacity was on an average 11% lower with propranolol than with placebo (p less than 0.001). The most marked reductions (20 and 33%) were found in the two patients with atrial fibrillation. The atrial rate in patients with sinus rhythm was significantly lower with propranolol than placebo both at rest (68 vs. 83 beats/min, p less than 0.001) and at maximal work load (91 vs. 141 beats/min, p less than 0.001). The present findings show that beta blockade has negative effects on exercise capacity in patients with complete heart block treated with VVI pacemakers. This finding should be considered in the selection of drug treatment in patients with fixed rate pacing and concomitant hypertension and/or ischemic heart disease.

  11. Contractile properties of early human embryonic stem cell-derived cardiomyocytes: beta-adrenergic stimulation induces positive chronotropy and lusitropy but not inotropy.

    Science.gov (United States)

    Pillekamp, Frank; Haustein, Moritz; Khalil, Markus; Emmelheinz, Markus; Nazzal, Rewa; Adelmann, Roland; Nguemo, Filomain; Rubenchyk, Olga; Pfannkuche, Kurt; Matzkies, Matthias; Reppel, Michael; Bloch, Wilhelm; Brockmeier, Konrad; Hescheler, Juergen

    2012-08-10

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.

  12. Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

    Directory of Open Access Journals (Sweden)

    Micha Hersch

    Full Text Available β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS addressing the values and susceptibility of cardiovascular-related traits to a selective β(1-blocker, Atenolol (ate, and a β-agonist, Isoproterenol (iso. The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA, a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8. An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6. Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD. Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

  13. Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon T; Hjelvang, Brian R

    2011-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Chronic heart failure (HF) is a syndrome with increasing prevalence. Though mortality is still high, the introduction of ß-adrenoceptor blockers for its treatment has improved survival considerably. • As is the case for all medical treatment, not all...... patients benefit from ß-adrenoceptor blocker treatment, and stratifying patients to different ß-adrenoceptor blockers by the use of pharmacogenomics might be of great value in improving HF therapy. • Previous studies have shown that the two single nucleotide polymorphisms (SNPs) ADRB1 Arg389Gly and ADRB2...... Gln27Glu interact with the ß-adrenoceptor blockers metoprolol and carvedilol, respectively. These interactions have led to stratified responses with regard to surrogate parameters, e.g. left ventricular ejection fraction (LVEF), pulse and blood pressure. • Several studies have failed to show...

  14. Post-Retrieval [beta]-Adrenergic Receptor Blockade: Effects on Extinction and Reconsolidation of Cocaine-Cue Memories

    Science.gov (United States)

    Fricks-Gleason, Ashley N.; Marshall, John F.

    2008-01-01

    Contexts and discrete cues associated with drug-taking are often responsible for relapse among addicts. Animal models have shown that interference with the reconsolidation of drug-cue memories can reduce seeking of drugs or drug-paired stimuli. One such model is conditioned place preference (CPP) in which an animal is trained to associate a…

  15. Receptor Expression in Rat Skeletal Muscle Cell Cultures

    Science.gov (United States)

    Young, Ronald B.

    1996-01-01

    One on the most persistent problems with long-term space flight is atrophy of skeletal muscles. Skeletal muscle is unique as a tissue in the body in that its ability to undergo atrophy or hypertrophy is controlled exclusively by cues from the extracellular environment. The mechanism of communication between muscle cells and their environment is through a group of membrane-bound and soluble receptors, each of which carries out unique, but often interrelated, functions. The primary receptors include acetyl choline receptors, beta-adrenergic receptors, glucocorticoid receptors, insulin receptors, growth hormone (i.e., somatotropin) receptors, insulin-like growth factor receptors, and steroid receptors. This project has been initiated to develop an integrated approach toward muscle atrophy and hypertrophy that takes into account information on the populations of the entire group of receptors (and their respective hormone concentrations), and it is hypothesized that this information can form the basis for a predictive computer model for muscle atrophy and hypertrophy. The conceptual basis for this project is illustrated in the figure below. The individual receptors are shown as membrane-bound, with the exception of the glucocorticoid receptor which is a soluble intracellular receptor. Each of these receptors has an extracellular signalling component (e.g., innervation, glucocorticoids, epinephrine, etc.), and following the interaction of the extracellular component with the receptor itself, an intracellular signal is generated. Each of these intracellular signals is unique in its own way; however, they are often interrelated.

  16. Personality effects on cardiovascular reactivity: need for closure moderates the impact of task difficulty on engagement-related myocardial beta-adrenergic activity.

    Science.gov (United States)

    Richter, Michael; Baeriswyl, Eric; Roets, Arne

    2012-05-01

    An experiment assessed the joint effect of dispositional need for closure (NFC) and task difficulty on engagement-related myocardial beta-adrenergic activity. Participants who scored either low or high on the NFC scale performed an ambiguous categorization task with either low or high difficulty. Confirming the theory-derived predictions, task difficulty effects on pre-ejection period (PEP) reactivity were moderated by NFC. If difficulty was low, PEP reactivity was low and independent of the participants' NFC level. If difficulty was high, participants with high NFC showed increased PEP reactivity compared to participants with low NFC. These results extend previous research on Wright's model of engagement-related cardiovascular reactivity and suggest that the model may provide a useful framework for assessing the impact of personality on cardiovascular response.

  17. The impact of beta-adrenergic blockade on daily rhythms of melatonin and body temperature of golden spiny mice Acomys russatus.

    Science.gov (United States)

    Haim, A; Zisapel, N

    1997-01-01

    Beta-adrenergic stimulation induces melatonin synthesis and non-shivering thermogenesis (NST) in rodents. The golden spiny mouse, Acomys russatus is a nocturnal species capable of diurnal activity when coexisting with its congenitor the common spiny mouse A. cahirinus. We have investigated the impact of beta-adrenergic blockade on 6-sulphatoxymelatonin (6-SMT--a metabolite and index of melatonin production) and body temperature (Tb) daily rhythms in male A. russatus. Mice were acclimated to an ambient temperature (Ta) of 28 degrees C, under two photoperiod regimes (16L:8D; 8L:16D). The daily rhythms of Tb and urinary 6-SMT were measured for a period of 30 h at intervals of 4 h. Propranolol (4.5 mg/kg, i.p.) was administered one hour before lights went off (i.e. when beta blockade does not affect NST in this species) and both variables were measured for another 30 h. The beta blocker markedly augmented melatonin output of A. russatus under both photoperiod regimes. The elevation in melatonin secretion was accompanied with an increase in Tb of only 16L:8D-acclimated mice (i.e. shorten duration of melatonin peak). However, in 8L:16D-acclimated mice, a phase advance of about 4 h was noted in 6-SMT daily rhythm. These results indicate that the role of sympathetic innervation in regulation of melatonin synthesis in A. russatus differs from that in the rat. In addition, these data are compatible with the hyperthermic action of melatonin in this species. Therefore, it is suggested that in A. russatus, other neural pathways are involved in its pineal regulation.

  18. Heart failure in very elderly population- a profile of heart failure in patients over the age of eighty

    Institute of Scientific and Technical Information of China (English)

    Christopher V.Chien; Dani Hackner; Ernst R. Schwarz

    2007-01-01

    Objective Heart failure is an epidemic in the elderly, but there is a striking lack of data in this clinically important patient population. We investigated the demographics, cardiac performance, and medication management of a segment of the hospital population in at least their eighth decade of life. Methods We retrospectively reviewed 75 records of heart failure patients who were 80 years of age or older. Records were reviewed for demographic information, presence or absence of diastolic dysfunction, evaluation of ejection fraction, and medication usage including angiotensin-concerting enzyme (ACE) inhibitors, angiotensin receptor antagonists (ARBs),beta-adrenergic blockers, digoxin, and aldosterone antagonists. Assessment for contra-indications to ACE inhibitor or ARBs use was also performed to assess co-morbidities that limit treatment of heart failure. Results The population of very elderly with heart failure is heterogeneous. We found a higher proportion of females as well as higher rates of diastolic dysfunction in patients aged ≥ 90 years compared to patients between the ages of 80-89 years. Usage of ACE inhibitors, ARBs and beta-adrenergic blockers was strikingly low throughout the very elderly population. While co-morbid conditions limited use of agents in many cases, there was a lack of explicit contra-indication in most patients not on an ACE inhibitor or an ARB. Conclusions Heart failure is not a single disease processes, but a continuum of disease processes that vary with age. The elderly with heart failure are an undertreated population, in part due to the multitude of co-morbidities that affect them. Further prospective studies are needed to better understand the physiology and ideal treatment regiment in this growing population.

  19. Beta-adrenergic signals regulate cardiac differentiation of mouse embryonic stem cells via mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yan, Lihui; Jia, Zhuqing; Cui, Jingjing; Yang, Hongtao; Yang, Huangtian; Zhang, Yongzhen; Zhou, Chunyan

    2011-08-01

    As embryonic stem cell-derived cardiomyocytes (ESC-CMs) have the potential to be used in cell replacement therapy, an understanding of the signaling mechanisms that regulate their terminal differentiation is imperative. In previous studies, we discovered the presence of adrenergic and muscarinic receptors in mouse embryonic stem cells (ESCs). However, little is known about the role of these receptors in cardiac differentiation and development, which is critically important in cardiac physiology and pharmacology. Here, we demonstrated that a β-adrenergic receptor (β-AR) agonist significantly enhanced cardiac differentiation as indicated by a higher percentage of beating embryoid bodies and a higher expression level of cardiac markers. Application of β1-AR and β2-AR antagonists partly abolished the effect of the β-AR agonist. In addition, by administering selective inhibitors we found that the effect of β-AR was driven via p38 mitogen-activated protein kinase and extracellular-signal regulated kinase pathway. These findings suggest that ESCs are also a target for β-adrenergic regulation and β-adrenergic signaling plays a role in ESC cardiac differentiation.

  20. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    Science.gov (United States)

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  1. The beta-adrenergic blocker carvedilol restores L-type calcium current in a myocardial infarction model of rabbit

    Institute of Scientific and Technical Information of China (English)

    LI Xia; HUANG Cong-xin; JIANG Hong; CAO Feng; WANG Teng

    2005-01-01

    Background Carvedilol, an antagonist of α1- and β-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.Methods After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot. Results The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33±0.45, n=25) compared to sham myocytes (6.52±0.21, n=20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91±0.39, n=20, P<0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 μmol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed. Conclusions The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.

  2. Neurohumoral activation in heart failure: the role of adrenergic receptors

    OpenAIRE

    Patricia C. Brum; Rolim, Natale P. L.; BACURAU, Aline V. N.; Alessandra Medeiros

    2006-01-01

    Heart failure (HF) is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardia...

  3. (S,S)- and (S,R)-1'-[{sup 18}F]fluorocarazolol, ligands for the visualization of pulmonary {beta}-adrenergic receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Elsinga, Philip H.; Vos, Marten G.; Waarde, Aren van; Braker, Anton H.; Groot, Tjibbe J. de; Anthonio, Rutger L.; Weemaes, Anne-Miek A.; Brodde, Otto-Erich; Visser, Gerben M.; Vaalburg, Willem

    1996-02-01

    The {beta}-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in the isopropyl group via a reductive alkylation by [{sup 18}F]-fluoroacetone of the corresponding (S)-desisopropyl compound according to a known procedure. The introduction of fluorine in the isopropyl group creates a new stereogenic centre resulting in the formation of (S,S)- and (S,R)-1'-[{sup 18}F]fluorocarazolol, which were separated by HPLC. Tissue distribution studies were performed in male Wistar rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mmol) showed high uptake in lung and heart, which could be blocked by pretreatment of the animals with ({+-})-propranolol. No significant differences were observed between the biodistribution of the two diastereomers. Metabolite analysis showed a rapid appearance of polar metabolites in plasma, while at 60 min postinjection 92% and 82% of the total radioactivity in lung and heart was unmetabolized 1'-[{sup 18}F]fluorocarazolol. In a PET-study with male Wistar rats, the lungs were clearly visualized and the pulmonary uptake was decreased after pretreatment of the animals with ({+-})-propranolol. The heart could not be visualized. Similar results were obtained in PET-studies with lambs.

  4. Metabolic response to various beta-adrenoceptor agonists in beta3-adrenoceptor knockout mice: evidence for a new beta-adrenergic receptor in brown adipose tissue.

    Science.gov (United States)

    Preitner, F; Muzzin, P; Revelli, J P; Seydoux, J; Galitzky, J; Berlan, M; Lafontan, M; Giacobino, J P

    1998-08-01

    The beta3-adrenoceptor plays an important role in the adrenergic response of brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic responses to beta-adrenoceptor stimulation were compared in adipose tissues of beta3-adrenoceptor knockout and wild type mice. The measured parameters were BAT fragment oxygen uptake (MO2) and isolated white adipocyte lipolysis. In BAT of wild type mice (-)-norepinephrine maximally stimulated MO2 4.1+/-0.8 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (dobutamine 5.1+/-0.3, terbutaline 5.3+/-0.3 and CL 316,243 4.8+/-0.9 fold, respectively); in BAT of beta3-adrenoceptor knockout mice, the beta1- and beta2-responses were fully conserved. In BAT of wild type mice, the beta1/beta2-antagonist and beta3-partial agonist CGP 12177 elicited a maximal MO2 response (4.7+/-0.4 fold). In beta3-adrenoceptor knockout BAT, this response was fully conserved despite an absence of response to CL 316,243. This unexpected result suggests that an atypical beta-adrenoceptor, distinct from the beta1-, beta2- and beta3-subtypes and referred to as a putative beta4-adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO2 stimulation. In isolated white adipocytes of wild type mice, (-)-epinephrine maximally stimulated lipolysis 12.1+/-2.6 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (TO509 12+/-2, procaterol 11+/-3, CL 316,243 11+/-3 fold, respectively) or with CGP 12177 (7.1+/-1.5 fold). In isolated white adipocytes of beta3-adrenoceptor knockout mice, the lipolytic responses to (-)epinephrine, to the beta1-, beta2-, beta3-adrenoceptor selective agonists and to CGP 12177 were almost or totally depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were conserved.

  5. Temporal coding by populations of auditory receptor neurons.

    Science.gov (United States)

    Sabourin, Patrick; Pollack, Gerald S

    2010-03-01

    Auditory receptor neurons of crickets are most sensitive to either low or high sound frequencies. Earlier work showed that the temporal coding properties of first-order auditory interneurons are matched to the temporal characteristics of natural low- and high-frequency stimuli (cricket songs and bat echolocation calls, respectively). We studied the temporal coding properties of receptor neurons and used modeling to investigate how activity within populations of low- and high-frequency receptors might contribute to the coding properties of interneurons. We confirm earlier findings that individual low-frequency-tuned receptors code stimulus temporal pattern poorly, but show that coding performance of a receptor population increases markedly with population size, due in part to low redundancy among the spike trains of different receptors. By contrast, individual high-frequency-tuned receptors code a stimulus temporal pattern fairly well and, because their spike trains are redundant, there is only a slight increase in coding performance with population size. The coding properties of low- and high-frequency receptor populations resemble those of interneurons in response to low- and high-frequency stimuli, suggesting that coding at the interneuron level is partly determined by the nature and organization of afferent input. Consistent with this, the sound-frequency-specific coding properties of an interneuron, previously demonstrated by analyzing its spike train, are also apparent in the subthreshold fluctuations in membrane potential that are generated by synaptic input from receptor neurons.

  6. Glucagon and plasma catecholamines during beta-receptor blockade in exercising man

    DEFF Research Database (Denmark)

    Galbo, H; Holst, Janett; Christensen, N J

    1976-01-01

    Seven men ran at 60% of individual maximal oxygen uptake to exhaustion during beta-adrenergic blockade with propranolol (P), during lipolytic blockade with nicotinic acid (N), or without drugs (C). The total work times (83 +/- 9 (P), 122 +/- 8 (N), 166 +/- 10 (C) min, mean and SE) differed...... decrease glucagon concentrations increased progressively in parallel with declining plasma glucose and were at exhaustion always three times preexercise values. Thus beta-adrenergic blockade did not diminish the glucagon response. Nor was this response increased when alpha-receptor stimulation in P...... experiments was intensified. Carbohydrate combustion was smaller and NEFA and glycerol concentrations in serum larger during C experiments. Alanine concentrations were never raised at exhaustion. Accordingly, neither stimulation of adrenergic receptors nor NEFA and alanine concentrations are major...

  7. Impaired beta-adrenergic response and decreased L-type calcium current of hypertrophied left ventricular myocytes in postinfarction heart failure

    Directory of Open Access Journals (Sweden)

    R.M. Saraiva

    2003-05-01

    Full Text Available Infarct-induced heart failure is usually associated with cardiac hypertrophy and decreased ß-adrenergic responsiveness. However, conflicting results have been reported concerning the density of L-type calcium current (I Ca(L, and the mechanisms underlying the decreased ß-adrenergic inotropic response. We determined I Ca(L density, cytoplasmic calcium ([Ca2+]i transients, and the effects of ß-adrenergic stimulation (isoproterenol in a model of postinfarction heart failure in rats. Left ventricular myocytes were obtained by enzymatic digestion 8-10 weeks after infarction. Electrophysiological recordings were obtained using the patch-clamp technique. [Ca2+]i transients were investigated via fura-2 fluorescence. ß-Adrenergic receptor density was determined by [³H]-dihydroalprenolol binding to left ventricle homogenates. Postinfarction myocytes showed a significant 25% reduction in mean I Ca(L density (5.7 ± 0.28 vs 7.6 ± 0.32 pA/pF and a 19% reduction in mean peak [Ca2+]i transients (0.13 ± 0.007 vs 0.16 ± 0.009 compared to sham myocytes. The isoproterenol-stimulated increase in I Ca(L was significantly smaller in postinfarction myocytes (Emax: 63.6 ± 4.3 vs 123.3 ± 0.9% in sham myocytes, but EC50 was not altered. The isoproterenol-stimulated peak amplitude of [Ca2+]i transients was also blunted in postinfarction myocytes. Adenylate cyclase activation through forskolin produced similar I Ca(L increases in both groups. ß-Adrenergic receptor density was significantly reduced in homogenates from infarcted hearts (Bmax: 93.89 ± 20.22 vs 271.5 ± 31.43 fmol/mg protein in sham myocytes, while Kd values were similar. We conclude that postinfarction myocytes from large infarcts display reduced I Ca(L density and peak [Ca2+]i transients. The response to ß-adrenergic stimulation was also reduced and was probably related to ß-adrenergic receptor down-regulation and not to changes in adenylate cyclase activity.

  8. Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells.

    Science.gov (United States)

    Miyamoto, K; Matsunaga, T; Takemoto, N; Sanae, F; Koshiura, R

    1985-05-01

    The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.

  9. Adrenergic receptor control mechanism for growth hormone secretion.

    Science.gov (United States)

    Blackard, W G; Heidingsfelder, S A

    1968-06-01

    The influence of catecholamines on growth hormone secretion has been difficult to establish previously, possibly because of the suppressive effect of the induced hyperglycemia on growth hormone concentrations. In this study, an adrenergic receptor control mechanism for human growth hormone (HGH) secretion was uncovered by studying the effects of alpha and beta receptor blockade on insulin-induced growth hormone elevations in volunteer subjects. Alpha adrenergic blockade with phentolamine during insulin hypoglycemia, 0.1 U/kg, inhibited growth hormon elevations to 30-50% of values in the same subjects during insulin hypoglycemia without adrenergic blockade. More complete inhibition by phentolamine could not be demonstrated at a lower dose of insulin (0.05 U/kg). Beta adrenergic blockade with propranolol during insulin hypoglycemia significantly enhanced HGH concentrations in paired experiments. The inhibiting effect of alpha adrenergic receptor blockade on HGH concentrations could not be attributed to differences in blood glucose or free fatty acid values; however, more prolonged hypoglycemia and lower plasma free fatty acid values may have been a factor in the greater HGH concentrations observed during beta blockade. In the absence of insulin induced hypoglycemia, neither alpha nor beta adrenergic receptor blockade had a detectable effect on HGH concentrations. Theophylline, an inhibitor of cyclic 3'5'-AMP phosphodiesterase activity, also failed to alter plasma HGH concentrations. These studies demonstrate a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on growth hormone secretion.

  10. Characterization and regulation of. beta. /sub 2/-adrenergic receptors in rat vas deferens

    Energy Technology Data Exchange (ETDEWEB)

    May, J.M.

    1985-01-01

    ..beta../sub 2/-Adrenergic receptors in rat vas deferens were examined by measuring the binding of /sup 125/I-pindolol (/sup 125/IPIN) to membrane preparations and the inhibition of evoked contractions in intact tissues. /sup 125/IPIN labeled a single class of binding sites with mass action kinetics. Affinity constants for ..beta..-adrenergic receptor antagonists calculated from both binding and functional experiments agreed well, suggesting that /sup 125/IPIN labels the functional ..beta../sub 2/-adrenergic receptor. n-Bromoacetylalprenololmenthane (BAAM) was used to decrease receptor density so that agonist affinity constants could be determined functionally. Treatment of tissues with BAAM decreased the functional potencies of agonists. Higher concentrations of BAAM decreased the maximum tissue response. Affinity constants for agonists calculated after BAAM treatment were compared to affinity constants determined from binding studies done under conditions designed to promote high or low affinity agonist binding. Functional affinity constants for isoproterenol and salbutamol agreed with the low affinity binding constants, suggesting that the low affinity form of the receptor initiates the functional response. Because acute denervation of vasa deferentia did not alter the density of /sup 125/IPIN binding sites, the sites are probably post-junctional. Chronic infusion of isoproterenol reduced the potency of isoproterenol, the maximum tissue response, and the receptor density. These results suggest that ..beta..-adrenergic receptor density and responsiveness in rat vas deferens are not affected by removing catecholamine sources, but receptor density and responsiveness can be decreased by increasing agonist concentration at the receptor.

  11. Stimulation of NTS A1 adenosine receptors evokes counteracting effects on hindlimb vasculature.

    Science.gov (United States)

    McClure, Joseph M; O'Leary, Donal S; Scislo, Tadeusz J

    2005-12-01

    Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of beta-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinejctions into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after beta-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the

  12. Beta adrenergic blockade reduces utilitarian judgement.

    Science.gov (United States)

    Terbeck, Sylvia; Sylvia, Terbeck; Kahane, Guy; Guy, Kahane; McTavish, Sarah; Sarah, McTavish; Savulescu, Julian; Julian, Savulescu; Levy, Neil; Neil, Levy; Hewstone, Miles; Miles, Hewstone; Cowen, Philip J

    2013-02-01

    Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 mg orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were 'up close and personal'. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel.

  13. Neurohumoral activation in heart failure: the role of adrenergic receptors

    Directory of Open Access Journals (Sweden)

    Patricia C. Brum

    2006-09-01

    Full Text Available Heart failure (HF is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardiac output. However, chronic exposure of the heart to elevated levels of catecholamines released from sympathetic nerve terminals and the adrenal gland may lead to further pathologic changes in the heart, resulting in continued elevation of sympathetic tone and a progressive deterioration in cardiac function. On a molecular level, altered beta-adrenergic receptor signaling plays a pivotal role in the genesis and progression of HF. beta-adrenergic receptor number and function are decreased, and downstream mechanisms are altered. In this review we will present an overview of the normal beta-adrenergic receptor pathway in the heart and the consequences of sustained adrenergic activation in HF. The myopathic potential of individual components of the adrenergic signaling will be discussed through the results of research performed in genetic modified animals. Finally, we will discuss the potential clinical impact of beta-adrenergic receptor gene polymorphisms for better understanding the progression of HF.A insuficiência cardíaca (IC é a via final comum da maioria das doenças cardiovasculares e uma das maiores causas de morbi-mortalidade. O desenvolvimento do estágio final da IC freqüentemente envolve um insulto inicial do miocárdio, reduzindo o débito cardíaco e levando ao aumento compensatório da atividade do sistema nervoso simpático (SNS. Existem evidências de que apesar da exposição aguda ser benéfica, exposições crônicas a elevadas concentra

  14. N-terminal {beta}{sub 2}-adrenergic receptor polymorphisms do not correlate with bronchodilator response in asthma families

    Energy Technology Data Exchange (ETDEWEB)

    Holyroyd, K.J.; Dragwa, C.; Xu, J. [Johns Hopkins Medical Institutions, Baltimore, MD (United States)] [and others

    1994-09-01

    Family and twin studies have suggested that susceptibility to asthma is inherited. One clinically relevant phenotype in asthma is the bronchodilator response to beta adrenergic therapy (reversibility) which may also be inherited and vary among asthmatics. Two polymorphisms of the {beta}{sub 2}-adrenergic receptor common to both asthmatic and normal individuals have been reported. One polymorphism, an amino acid polymorphism at position 16, correlated in one study with the need for long-term corticosteriod use in a population of asthmatics. It is conceivable that the increased use of corticosteroids needed to control symptoms in these patients may be explained by a decreased responsiveness to brochodilators mediated through this amino acid polymorphism in the {beta}{sub 2}-adrenergic receptor. However, the response to {beta}{sub 2} bronchodilators was not tested in these patients. In our Dutch asthma families, DNA sequencing of the {beta}{sub 2}-adrenergic receptor has been performed for N-terminal polymorphisms at amino acid positions 16 and 27 in over 100 individuals, and no correlation was found with the increase of FEV{sub 1} in response to bronchodilator. Linkage analysis between bronchodilator response and marker D5S412 near the {beta}{sub 2}-adrenergic receptor gene was performed in 286 sibpairs from these families. Using a bronchodilator response of >10% in FEV{sub 1} as a qualitative definition of affected individuals, there were 145 unaffected sibpairs, 121 sibpairs where one was affected, and 20 in which both were affected. Linear regression analysis of these sibpair data suggested possible linkage (p=0.007). This supports further examination of the {beta}{sub 2}-adrenergic receptor and its regulatory regions for polymorphisms that correlate with the bronchodilator response in asthma families.

  15. Melanocortin-1 receptor gene variants in four Chinese ethnic populations

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    There is strong relationship between melanocortin-1 receptor (MC1R) gene variants and human hair color and skin type.Based on a sequencing study of MC1R gene in 50 individuals from the Uygur,Tibetan,Wa and Dai ethnic populations,we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu,Arg67Gln,Val92Met,Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G),among which C414T and Ala299Val were reported for the first time.Confirmation and analysis were also made of 122 individuals at three common point mutations (Val92Met,Arg163Gln,A942G) using PCR-SSCP.The frequency of Arg163Gln variant varies in the four ethnic populations,with percentage of 40%,85.0%,66.2% and 72.7%,respectively,while those of Val92Met and A942G are roughly similar in these four populations.The different environments,migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

  16. Neurotransmitter receptor-mediated signaling pathways as modulators of carcinogenesis.

    Science.gov (United States)

    Schuller, Hildegard M

    2007-01-01

    The autonomic nervous system with its two antagonistic branches, the sympathicus and the parasympathicus, regulates the activities of all body functions that are not under voluntary control. While the autonomic regulation of organ functions has been extensively studied, little attention has been given to the potential role of neurohumoral transmission at the cellular level in the development of cancer. Studies conducted by our laboratory first showed that binding of the parasympathetic neurotransmitter, acetylcholine, as well as nicotine or its nitrosated cancer-causing derivative, NNK, to nicotinic acetylcholine receptors comprised of alpha7 subunits activated a mitogenic signal transduction pathway in normal and neoplastic pulmonary neuroendocrine cells. On the other hand, beta-adrenergic receptors (Beta-ARs), which transmit signals initiated by binding of the catecholamine neurotransmitters of the sympathicus, were identified by our laboratory as important regulators of cell proliferation in cell lines derived from human adenocarcinomas of the lungs, pancreas, and breast. The tobacco-specific carcinogen NNK bound with high affinity to Beta1- and Beta2-ARs, thus activating cAMP, protein kinase A, and the transcription factor CREB. Collectively, neurotransmitter receptors of the nicotinic and Beta-adrenergic families appear to regulate cellular functions essential for the development and survival of the most common human cancers.

  17. A comparison of locomotor responses to some psychotropic drugs and cerebral receptors in the Acomys cahirinus and the laboratory mouse.

    Science.gov (United States)

    Marona-Lewicka, D; Michaluk, J; Antkiewicz-Michaluk, L; Vetulani, J

    1987-01-01

    Comparative studies of the laboratory mouse and Acomys cahirinus have shown differences in their motor activity patterns and motor responses to morphine, apomorphine and clonidine. The two species also differed in respect of the density of cerebral alpha 2-adrenergic receptors, but no significant differences between other types of receptors (alpha 1-adrenergic, beta-adrenergic, opiate mu and delta, and spiroperidol binding sites) were found. It is suggested that the high excitability of the Acomys may be related to a deficit in the inhibitory noradrenergic transmission in the central nervous system.

  18. Spinal GABA-B receptor modulates neutrophil recruitment to the knee joint in zymosan-induced arthritis.

    Science.gov (United States)

    Bassi, Gabriel S; do C Malvar, David; Cunha, Thiago M; Cunha, Fernando Q; Kanashiro, Alexandre

    2016-08-01

    Recent studies have demonstrated that the central nervous system controls inflammatory responses by activating complex efferent neuroimmune pathways. The present study was designed to evaluate the role that central gamma-aminobutyric acid type B (GABA-B) receptor plays in neutrophil migration in a murine model of zymosan-induced arthritis by using different pharmacological tools. We observed that intrathecal administration of baclofen, a selective GABA-B agonist, exacerbated the inflammatory response in the knee after zymosan administration characterized by an increase in the neutrophil recruitment and knee joint edema, whereas saclofen, a GABA-B antagonist, exerted the opposite effect. Intrathecal pretreatment of the animals with SB203580 (an inhibitor of p38 mitogen-activated protein kinase) blocked the pro-inflammatory effect of baclofen. On the other hand, systemic administration of guanethidine, a sympatholytic drug that inhibits catecholamine release, and nadolol, a beta-adrenergic receptor antagonist, reversed the effect of saclofen. Moreover, saclofen suppressed the release of the pro-inflammatory cytokines into the knee joint (ELISA) and pain-related behaviors (open field test). Since the anti-inflammatory effect of saclofen depends on the sympathetic nervous system integrity, we observed that isoproterenol, a beta-adrenergic receptor agonist, mimics the central GABA-B blockade decreasing knee joint neutrophil recruitment. Together, these results demonstrate that the pharmacological manipulation of spinal GABAergic transmission aids control of neutrophil migration to the inflamed joint by modulating the activation of the knee joint-innervating sympathetic terminal fibers through a mechanism dependent on peripheral beta-adrenergic receptors and central components, such as p38 MAPK.

  19. [Regulation of G protein-coupled receptor kinase activity].

    Science.gov (United States)

    Haga, T; Haga, K; Kameyama, K; Nakata, H

    1994-09-01

    Recent progress on the activation of G protein-coupled receptor kinases is reviewed. beta-Adrenergic receptor kinase (beta ARK) is activated by G protein beta gamma -subunits, which interact with the carboxyl terminal portion of beta ARK. Muscarinic receptor m2-subtypes are phosphorylated by beta ARK1 in the central part of the third intracellular loop (I3). Phosphorylation of I3-GST fusion protein by beta ARK1 is synergistically stimulated by the beta gamma -subunits and mastoparan or a peptide corresponding to portions adjacent to the transmembrane segments of m2-receptors or by beta gamma -subunits and the agonist-bound I3-deleted m2 variant. These results indicate that agonist-bound receptors serve as both substrates and activators of beta ARK.

  20. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...... and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype....

  1. Enhanced negative chronotropy by inhibitory receptors in transgenic heart overexpressing beta(2)-adrenoceptors.

    Science.gov (United States)

    Du, X J; Vincan, E; Percy, E; Woodcock, E A

    2000-03-15

    Transgenic (TG) mice overexpressing beta(2)-adrenoceptors (AR) in the heart have enhanced beta-adrenergic activity. Since the degree of beta-adrenergic activation influences the negative chronotropic control of heart rate (HR), we studied the inhibitory effect of cholinergic and purinergic stimulation on HR in TG and wild-type (WT) control mice. Bradycardia in response to vagal nerve stimulation and administration of acetylcholine or adenosine was studied in anesthetised animals and perfused hearts. Basal HR was significantly higher in TG than WT mice (P<0.01). Electrical stimulation of vagal nerves (1-32 Hz) induced a Hz-dependent reduction in HR and the response was more pronounced in TG than WT groups (P<0.01). In perfused hearts, HR reduction by acetylcholine (ACh) was more pronounced with EC(50) 110-fold lower in TG than WT hearts. Adenosine-induced bradycardia, which was abolished by a P(1) antagonist, was more pronounced in TG hearts. After pre-treatment with pertussis toxin (PT, 100 microg/kg), bradycardia by vagal nerve stimulation or ACh remained unchanged in WT, but markedly inhibited in TG hearts (both P<0.01). Conversely, inhibiting guanylyl cyclase with LY83583 (30 microM) or nitric oxide synthase with L-NMMA (100 microM) attenuated HR reduction by vagal nerve stimulation in WT but not in TG hearts. Immunobloting assay showed similar G(ialpha2) abundance in TG and WT hearts. Thus, cardiac overexpression of beta(2)AR with high beta-adrenergic activity leads to hypersensitivity of inhibitory receptors controlling HR due to increase in activity of PT-sensitive G-proteins.

  2. Yeast as a model system for mammalian seven-transmembrane segment receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jeansonne, N.E. [East Carolina Univ. Medical School, Greenville, NC (United States)

    1994-05-01

    Investigators have used the budding yeast Saccharomyces cerevisiae as a model system in which to study the {beta}-adrenergic receptor, the T-cell receptor pathway, initiation of mammalian DNA replication, initiation of mammalian transcription, secretion, the CDC2 kinase system, cell cycle control, and aging, as well as the function of oncogenes. This list continues to growth with the discovery of an immunoglobulin heavy-chain binding homologue in yeast, an Rb binding protein homologue, and a possible yeast arrestin. Yeast is relatively easy to maintain, to grow, and to genetically manipulate. A single gene can be overexpressed, selectively mutated or deleted from its chromosomal location. In this way, the in vivo function of a gene can be studied. It has become reasonable to consider yeast as a model system for studying the seven transmembrane segments (7-TMS) receptor family. Currently, subtypes of the {beta}-adrenergic receptor are being studied in yeast. The receptor and its G{sub {alpha}}-G-protein, trigger the mating pheromone receptor pathway. This provides a powerful assay for determining receptor function. Studies expressing the muscarinic cholinergic receptor in yeast are underway. The yeast pheromone receptor belongs to this receptor family, sharing sequences and secondary structure homology. An effective strategy has been to identify a yeast pathway or process which is homologous to a mammalian system. The pathway is delineated in yeast, identifying other genetic components. Then yeast genes are used to screen for human homologues of these components. The putative human homologues are then expressed in yeast and in mammalian cells to determine function. When this type of {open_quotes}mixing and matching{close_quotes} works, yeast genetics can be a powerful tool. 115 refs.

  3. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...

  4. The role of adrenergic receptors in the motility of duodenum and choledochoduodenal junction in the pig.

    Science.gov (United States)

    Blichowski, A; Andrzejewski, W; Gaszyński, W; Kozulski, W

    1977-01-01

    The role of adenergic receptors in the motility of duodenum and choledochoduodenal junction in the pig. Acta Physiol. Pol., 1977, 28 (6): 521-528. The choldeochoduodenal junction in the Vietnamese pig is functionally and anatomically a part of duodenal wall. In view of this, investigations were carried out for establishing the role of adrenergic receptors in the development of motor function of this part of the intestinal tract. The experiments were performed on domestic Vietnamese pigs (Sus scrofa domestica) and they showed that after stimulation of alpha and beta adrenergic receptors the motor activity of the duodenal muscular coat and the choledochoduodenal junction is inhibited. The obtained results suggest similar reactions of the adrenergic receptors in both examined parts of the intestinal tract in the pig.

  5. Neural network analysis of the information content in population responses from human periodontal receptors

    Science.gov (United States)

    Edin, Benoni B.; Trulsson, Mats

    1992-07-01

    Understanding of the information processing in some sensory systems is hampered for several reasons. First, some of these systems may depend on several receptor types with different characteristics, and the crucial features of natural stimuli encoded by the receptors are rarely known with certainty. Second, the functional output of sensory processing is often not well defined. The human tooth is endowed with several types of sensory receptors. Among these, the mechanoreceptors located in the periodontal ligaments have been implicated in force encoding during chewing and biting. Individual receptors cannot, however, code unambiguously either the direction or the magnitude of the applied forces. Neuronal responses recorded in single human nerve fibers from periodontal receptors were fed to multi-layered feed-forward networks. The networks were trained with error back-propagation to identify specific features of the force stimuli that evoked the receptor responses. It was demonstrated that population responses in periodontal receptors contain information about both the point of attack and the direction of applied forces. It is concluded that networks may provide a powerful tool to investigate the information content in responses from biological receptor populations. As such, specific hypotheses with respect to information processing may be tested using neural networks also in sensory systems less well understood than, for instance, the visual system.

  6. Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2.

    Science.gov (United States)

    Tsuga, H; Kameyama, K; Haga, T; Kurose, H; Nagao, T

    1994-12-23

    Sequestration of m2 receptors (muscarinic acetylcholine receptor m2 subtypes), which was assessed as loss of N-[3H]methylscopolamine ([3H]NMS) binding activity from the cell surface, was examined in COS 7 and BHK-21 cells that had been transfected with expression vectors encoding the m2 receptor and, independently, vectors encoding a G protein-coupled receptor kinase (GRK2) (beta-adrenergic receptor kinase 1) or a GRK2 dominant-negative mutant (DN-GRK2). The sequestration of m2 receptors became apparent when the cells were treated with 10(-5) M or higher concentrations of carbamylcholine. In this case, approximately 40% or 20-25% of the [3H]NMS binding sites on COS 7 or BHK-21 cells, respectively, were sequestered with a half-life of 15-25 min. In cells in which GRK2 was also expressed, the sequestration became apparent in the presence of 10(-7) M carbamylcholine. Approximately 40% of the [3H]NMS binding sites on both COS 7 and BHK-21 cells were sequestered in the presence of 10(-6) M or higher concentrations of carbamylcholine. When DN-GRK2 was expressed in COS 7 cells, the proportion of [3H]NMS binding sites sequestered in the presence of 10(-5) M or higher concentrations of carbamylcholine was reduced to 20-30%. These results indicate that the phosphorylation of m2 receptors by GRK2 facilitates their sequestration. These results are in contrast with the absence of a correlation between sequestration and the phosphorylation of beta-adrenergic receptors by the GRK2 and suggests that the consequences of phosphorylation by GRK2 are different for different receptors.

  7. Mechanisms of immune regulation by norepinephrine and cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of {beta}-adrenergic receptors. The role of {beta}-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective {beta}-adrenergic antagonists. The antagonists were metoprolol ({beta}{sub 1}-selective), ICI 118-551 ({beta}{sub 2}-selective), and propranolol ({beta}-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, ({sup 3}H)CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% {beta}{sub 2}- and 25% {beta}{sub 1}-adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% {beta}{sub 2}-adrenergic receptors, while enriched B lymphocytes contained 90% {beta}{sub 2}-adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% {beta}{sub 2}-receptors, while 100% were {beta}{sub 2} receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous {beta}-adrenergic receptor population on T lymphocytes and a more homogeneous {beta}{sub 2}-population on B lymphocytes.

  8. Scavenger receptor AI/II truncation, lung function and COPD: a large population-based study

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjærg-Hansen, Anne

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...... whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population....

  9. Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor cell surface stability.

    Science.gov (United States)

    Fairfax, Benjamin P; Pitcher, Julie A; Scott, Mark G H; Calver, Andrew R; Pangalos, Menelas N; Moss, Stephen J; Couve, Andrés

    2004-03-26

    GABA(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. The dynamic control of the cell surface stability of GABA(B) receptors is likely to be of fundamental importance in the modulation of receptor signaling. Presently, however, this process is poorly understood. Here we demonstrate that GABA(B) receptors are remarkably stable at the plasma membrane showing little basal endocytosis in cultured cortical and hippocampal neurons. In addition, we show that exposure to baclofen, a well characterized GABA(B) receptor agonist, fails to enhance GABA(B) receptor endocytosis. Lack of receptor internalization in neurons correlates with an absence of agonist-induced phosphorylation and lack of arrestin recruitment in heterologous systems. We also demonstrate that chronic exposure to baclofen selectively promotes endocytosis-independent GABA(B) receptor degradation. The effect of baclofen can be attenuated by activation of cAMP-dependent protein kinase or co-stimulation of beta-adrenergic receptors. Furthermore, we show that increased degradation rates are correlated with reduced receptor phosphorylation at serine 892 in GABA(B)R2. Our results support a model in which GABA(B)R2 phosphorylation specifically stabilizes surface GABA(B) receptors in neurons. We propose that signaling pathways that regulate cAMP levels in neurons may have profound effects on the tonic synaptic inhibition by modulating the availability of GABA(B) receptors.

  10. Association between peroxisome proliferator-activated receptor gene single nucleotide polymorphisms and arterial stiffness in adult Chinese population

    Institute of Scientific and Technical Information of China (English)

    许如意

    2013-01-01

    Objective To analyze the association between single nucleotide polymorphisms(SNPs) of peroxisome proliferator-activated receptor(PPAR)and arterial stiffness in adult Chinese population(>50 years).Methods

  11. Macroscopic law of conservation revealed in the population dynamics of Toll-like receptor signaling

    Directory of Open Access Journals (Sweden)

    Selvarajoo Kumar

    2011-04-01

    Full Text Available Abstract Stimulating the receptors of a single cell generates stochastic intracellular signaling. The fluctuating response has been attributed to the low abundance of signaling molecules and the spatio-temporal effects of diffusion and crowding. At population level, however, cells are able to execute well-defined deterministic biological processes such as growth, division, differentiation and immune response. These data reflect biology as a system possessing microscopic and macroscopic dynamics. This commentary discusses the average population response of the Toll-like receptor (TLR 3 and 4 signaling. Without requiring detailed experimental data, linear response equations together with the fundamental law of information conservation have been used to decipher novel network features such as unknown intermediates, processes and cross-talk mechanisms. For single cell response, however, such simplicity seems far from reality. Thus, as observed in any other complex systems, biology can be considered to possess order and disorder, inheriting a mixture of predictable population level and unpredictable single cell outcomes.

  12. Cannabinoid Type-1 Receptor Gene Polymorphisms Are Associated with Central Obesity in a Southern Brazilian Population

    Directory of Open Access Journals (Sweden)

    Janaína P. Jaeger

    2008-01-01

    Full Text Available The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1 gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353, 3813A/G (rs12720071 and 4895A/G (rs806368 polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR (P = 0.014; P = 0.042 after Bonferroni correction. An additive effect with the GAA haplotype was associated with WHR (P = 0.028, although this statistical significance disappeared after Bonferroni correction (P = 0.084. No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 gene polymorphism is associated with central obesity in this Brazilian population of European ancestry.

  13. [Takotsubo cardiomyopathy: a novel beta-adrenergic blocker withdrawal syndrome].

    Science.gov (United States)

    Tomcsányi, János; Jávor, Kinga; Arabadzisz, Hrisula; Zsoldos, András; Wagner, Vince; Sármán, Balázs

    2013-02-17

    The authors describe two cases of takotsubo cardiomyopathy developing after an abrupt withdrawal of carvedilol and bisoprolol. Takotsubo or stress cardiomyopathy is characterized by acute and reversible cardiac dysfunction without coronary artery disease. It is triggered by acute emotional or physical stress, drugs or drug withdrawal. The immediate discontinuation of the long acting vasodilator beta-blocker, carvedilol has not yet been described to cause takotsubo cardiomyopathy. The authors recommend cautious withdrawal of beta-blockers.

  14. Drift, not selection, shapes toll-like receptor variation among oceanic island populations.

    Science.gov (United States)

    Gonzalez-Quevedo, Catalina; Spurgin, Lewis G; Illera, Juan Carlos; Richardson, David S

    2015-12-01

    Understanding the relative role of different evolutionary forces in shaping the level and distribution of functional genetic diversity among natural populations is a key issue in evolutionary and conservation biology. To do so accurately genetic data must be analysed in conjunction with an unambiguous understanding of the historical processes that have acted upon the populations. Here, we focused on diversity at toll-like receptor (TLR) loci, which play a key role in the vertebrate innate immune system and, therefore, are expected to be under pathogen-mediated selection. We assessed TLR variation within and among 13 island populations (grouped into three archipelagos) of Berthelot's pipit, Anthus berthelotii, for which detailed population history has previously been ascertained. We also compared the variation observed with that found in its widespread sister species, the tawny pipit, Anthus campestris. We found strong evidence for positive selection at specific codons in TLR1LA, TLR3 and TLR4. Despite this, we found that at the allele frequency level, demographic history has played the major role in shaping patterns of TLR variation in Berthelot's pipit. Levels of diversity and differentiation within and across archipelagos at all TLR loci corresponded very closely with neutral microsatellite variation and with the severity of the bottlenecks that occurred during colonization. Our study shows that despite the importance of TLRs in combating pathogens, demography can be the main driver of immune gene variation within and across populations, resulting in patterns of functional variation that can persist over evolutionary timescales.

  15. Androgen receptor CAG polymorphism and the risk of benign prostatic hyperplasia in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Vanderlei Biolchi

    2012-06-01

    Full Text Available Benign prostatic hyperplasia (BPH is a very frequent age-related proliferative abnormality in men. Polymorphic CAG repeat in the androgen receptor (AR can alter transactivation of androgen-responsive genes and potentially influence BPH risk. We investigated the association between CAG repeat length and risk of BPH in a case-control study of a Brazilian population. We evaluated 214 patients; 126 with BPH and 88 healthy controls. DNA was extracted from peripheral leucocytes and the AR gene was analyzed using fragment analysis. Hazard ratio (HR and 95% confidence interval were estimated using logistic regression models. Mean CAG length was not different between patients with BPH and controls. The CAG repeat length was examined as a categorical variable (CAG 21 and CAG 22 and did not differ between the control vs. the BPH group. We found no evidence for an association between AR CAG repeat length in BPH risk in a population-based sample of Brazilians.

  16. Sleeping Beauty Transposition of Chimeric Antigen Receptors Targeting Receptor Tyrosine Kinase-Like Orphan Receptor-1 (ROR1 into Diverse Memory T-Cell Populations.

    Directory of Open Access Journals (Sweden)

    Drew C Deniger

    Full Text Available T cells modified with chimeric antigen receptors (CARs targeting CD19 demonstrated clinical activity against some B-cell malignancies. However, this is often accompanied by a loss of normal CD19+ B cells and humoral immunity. Receptor tyrosine kinase-like orphan receptor-1 (ROR1 is expressed on sub-populations of B-cell malignancies and solid tumors, but not by healthy B cells or normal post-partum tissues. Thus, adoptive transfer of T cells specific for ROR1 has potential to eliminate tumor cells and spare healthy tissues. To test this hypothesis, we developed CARs targeting ROR1 in order to generate T cells specific for malignant cells. Two Sleeping Beauty transposons were constructed with 2nd generation ROR1-specific CARs signaling through CD3ζ and either CD28 (designated ROR1RCD28 or CD137 (designated ROR1RCD137 and were introduced into T cells. We selected for T cells expressing CAR through co-culture with γ-irradiated activating and propagating cells (AaPC, which co-expressed ROR1 and co-stimulatory molecules. Numeric expansion over one month of co-culture on AaPC in presence of soluble interleukin (IL-2 and IL-21 occurred and resulted in a diverse memory phenotype of CAR+ T cells as measured by non-enzymatic digital array (NanoString and multi-panel flow cytometry. Such T cells produced interferon-γ and had specific cytotoxic activity against ROR1+ tumors. Moreover, such cells could eliminate ROR1+ tumor xenografts, especially T cells expressing ROR1RCD137. Clinical trials will investigate the ability of ROR1-specific CAR+ T cells to specifically eliminate tumor cells while maintaining normal B-cell repertoire.

  17. Sleeping Beauty Transposition of Chimeric Antigen Receptors Targeting Receptor Tyrosine Kinase-Like Orphan Receptor-1 (ROR1) into Diverse Memory T-Cell Populations

    Science.gov (United States)

    Deniger, Drew C.; Yu, Jianqiang; Huls, M. Helen; Figliola, Matthew J.; Mi, Tiejuan; Maiti, Sourindra N.; Widhopf, George F.; Hurton, Lenka V.; Thokala, Radhika; Singh, Harjeet; Olivares, Simon; Champlin, Richard E.; Wierda, William G.; Kipps, Thomas J.; Cooper, Laurence J. N.

    2015-01-01

    T cells modified with chimeric antigen receptors (CARs) targeting CD19 demonstrated clinical activity against some B-cell malignancies. However, this is often accompanied by a loss of normal CD19+ B cells and humoral immunity. Receptor tyrosine kinase-like orphan receptor-1 (ROR1) is expressed on sub-populations of B-cell malignancies and solid tumors, but not by healthy B cells or normal post-partum tissues. Thus, adoptive transfer of T cells specific for ROR1 has potential to eliminate tumor cells and spare healthy tissues. To test this hypothesis, we developed CARs targeting ROR1 in order to generate T cells specific for malignant cells. Two Sleeping Beauty transposons were constructed with 2nd generation ROR1-specific CARs signaling through CD3ζ and either CD28 (designated ROR1RCD28) or CD137 (designated ROR1RCD137) and were introduced into T cells. We selected for T cells expressing CAR through co-culture with γ-irradiated activating and propagating cells (AaPC), which co-expressed ROR1 and co-stimulatory molecules. Numeric expansion over one month of co-culture on AaPC in presence of soluble interleukin (IL)-2 and IL-21 occurred and resulted in a diverse memory phenotype of CAR+ T cells as measured by non-enzymatic digital array (NanoString) and multi-panel flow cytometry. Such T cells produced interferon-γ and had specific cytotoxic activity against ROR1+ tumors. Moreover, such cells could eliminate ROR1+ tumor xenografts, especially T cells expressing ROR1RCD137. Clinical trials will investigate the ability of ROR1-specific CAR+ T cells to specifically eliminate tumor cells while maintaining normal B-cell repertoire. PMID:26030772

  18. Estrogen receptor gene polymorph ism in a Chinese population with multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Qingli Sun; Ruping Xie; Yu Fu; Xiaogang Li; Dongsheng Fan

    2011-01-01

    This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis,and 95 ethnicity-matched controls.using polymerase chain reaction-restriction fragment-length polymorphism analysis.The results revealed that the P allele of Pvull was significantly more prevalent in multiple sclerosis patients compared with controls(P=0.019).While distribution frequencies were significantly increased in female multiple sclerosis patients compared with female controls(P=0.044),no significant difference was observed between male patients and controls(P>0.05).Frequencies of Ppxx genotypes were significantly higher in multiple sclerosis patients compared with controls(24.3%VS.12.8%,P=0.025).Genotypes and alleles of the estrogen receptor were not associated with age.number of attacks or expanded disability status scale scores of patients with multiple sclerosis.These findings jndicate that the PVUll but not the Xbal polymorphism in the estrogen receptor gene iS associated with susceptibility to multiple sclerosis in the Chinese population.in addition.women with P allele appear to be particularly susceptible to multiple sclerosis.

  19. Genetic diversity of bitter taste receptor gene family in Sichuan domestic and Tibetan chicken populations

    Indian Academy of Sciences (India)

    YUAN SU; DIYAN LI; UMA GAUR; YAN WANG; NAN WU; BINLONG CHEN; HONGXIAN XU; HUADONG YIN; YAODONG HU; QING ZHU

    2016-09-01

    The sense of bitter taste plays a critical role in animals as it can help them to avoid intake of toxic and harmful substances. Previous research had revealed that chicken has only three bitter taste receptor genes (Tas2r1, Tas2r2 and Tas2r7). To better understand the genetic polymorphisms and importance of bitter taste receptor genes (Tas2rs) in chicken, here, we sequenced Tas2rs of 30 Sichuan domestic chickens and 30 Tibetan chickens. Thirteen single-nucleotide polymorphisms (SNPs) including three nonsynonymous mutations (m.359G>C, m.503C > A and m.583A>G) were detected in Tas2r1 (m. is the abbreviation for mutation); three SNPs were detected in Tas2r2, but none of them were missense mutation; eight SNPs were detected in Tas2r7 including six nonsynonymous substitutions (m.178G>A, m.421A> C, m.787C>T, m.832G > T, m.907A> T and m.943G >A). Tajima’s D neutral test indicates that there is no population expansion in both populations, and the size of the population is relatively stable. All the three networks indicate that red jungle fowls share haplotypes with domestic chickens. In addition, we found that haplotypes H1 and HE1 were positively associated with high-altitude adaptation, whereas haplotypes H4 and HE4 showed a negative correlation with high-altitude adaptation in Tas2rs. Although, chicken has only three Tas2rs, our results showed that both Sichuan domestic chickens and Tibetan chickens have abundant haplotypes in Tas2rs, especially in Tas2r7, which might help chickens to recognize a wide variety of bitter-tasting compounds.

  20. Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor-effector coupling.

    Science.gov (United States)

    Couve, A; Thomas, P; Calver, A R; Hirst, W D; Pangalos, M N; Walsh, F S; Smart, T G; Moss, S J

    2002-05-01

    GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). Basal phosphorylation of this residue is evident in rat brain membranes and in cultured neurons. Phosphorylation of Ser892 is modulated positively by pathways that elevate cAMP concentration, such as those involving forskolin and beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor phosphorylation, which is consistent with PKA functioning in the control of GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892 specifically enhances the membrane stability of GABA(B) receptors. We conclude that signaling pathways that activate PKA may have profound effects on GABA(B) receptor-mediated synaptic inhibition. These results also challenge the accepted view that phosphorylation is a universal negative modulator of G protein-coupled receptors.

  1. Ontogeny of catecholamine and adenosine receptor-mediated cAMP signaling of embryonic red blood cells: role of cGMP-inhibited phosphodiesterase 3 and hemoglobin.

    Science.gov (United States)

    Baumann, R; Blass, C; Götz, R; Dragon, S

    1999-12-15

    We have previously shown that the cAMP signaling pathway controls major aspects of embryonic red blood cell (RBC) function in avian embryos (Glombitza et al, Am J Physiol 271:R973, 1996; and Dragon et al, Am J Physiol 271:R982, 1996) that are important for adaptation of the RBC gas transport properties to the progressive hypercapnia and hypoxia of later stages of avian embryonic development. Data about the ontogeny of receptor-mediated cAMP signaling are lacking. We have analyzed the response of primitive and definitive chick embryo RBC harvested from day 3 to 18 of development towards forskolin, beta-adrenergic, and A2 receptor agonists. The results show a strong response of immature definitive and primitive RBC to adenosine A2 and beta-adrenergic receptor agonists, which is drastically reduced in the last stage of development, coincident with the appearance of mature, transcriptionally inactive RBC. Modulation of cGMP-inhibited phosphodiesterase 3 (PDE3) has a controlling influence on cAMP accumulation in definitive RBC. Under physiological conditions, PDE3 is inhibited due to activation of soluble guanylyl cyclase (sGC). Inhibition of sGC with the specific inhibitor ODQ decreases receptor-mediated stimulation of cAMP production; this effect is reversed by the PDE3 inhibitor milrinone. sGC is acitivated by nitric oxide (NO), but we found no evidence for production of NO by erythrocyte NO-synthase. However, embryonic hemoglobin releases NO in an oxygen-linked manner that may activate guanylyl cyclase.

  2. Association between Polymorphism of Interleukin-23 Receptor and Hashimoto's Thyroiditis in Chinese Han Population of Shandong

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Li; Jie Han; Yu-Fei Wang; Jun Dai; Hui Zhang; Chun-Xia Li; Qun Ma

    2015-01-01

    Objective:The interleukin-23 receptor (IL-23R) has been shown to be associated with autoimmune diseases in many different populations.This study aimed to investigate the association between IL-23R gene polymorphism and susceptibility to Hashimoto's thyroiditis (HT) in Chinese Han population of Shandong.Methods:A case-control cohort study was performed in 145 HT patients from First People's Hospital of Jining between February 2010 to October 2013 and 150 healthy controls.Two single nucleotide polymorphisms located in the promoter region ofIL-23R gene (rs 17375018 and rs7517847) were examined by polymerase chain reaction-restriction fragment length polymorphism analysis.Hardy-Weinberg equilibrium was performed using the Chi-square test.Genotype frequencies were estimated by direct counting,and allele and genotype frequencies between patients and controls were analyzed by the Chi-square test.Results:The rs 17375018 GG genotype and the G allele were significantly increased in HT patients compared with healthy controls (P =0.034 and P =0.013,respectively).No association was identified between HT patients and healthy controls in rs7517847.Conclusion:The study demonstrated that polymorphism of IL-23R gene rs17375018 is highly associated with HT in Chinese Han population of Shandong,suggesting that IL-23R gene polymorphism (rs 17375018 G) may play a critical role in susceptibility to HT.

  3. 29. LACK OF ASSOCIATION OF AH RECEPTOR GENE POLYMORPHISM WITH SUSCEPTIBILITY TO BLADDER CANCER IN SHANGHAI POPULATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@The diversity in genetic background largely predetermine the individual susceptibility towards health risk related to xenobiotic exposure. The receptors of signal transduction mechanism are involved in the modulation of toxicological outcome of xenobiotics. The survey of distribution of different polymorphic forms of Ah receptor in Chinese population and probing into their possible association with health risk related with xenobiotic exposure will not only contribute to a better understanding of mechanism of imperilment, but also inspire a clue for a further

  4. Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations

    NARCIS (Netherlands)

    Jenab, Mazda; McKay, James; Bueno-de-Mesquita, Hendrik B.; van Duijnhoven, Franzel J. B.; Ferrari, Pietro; Slimani, Nadia; Jansen, Eugene H. J. M.; Pischon, Tobias; Rinaldi, Sabina; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Engel, Pierre; Kaaks, Rudolf; Linseisen, Jakob; Boeing, Heiner; Fisher, Eva; Trichopoulou, Antonia; Dilis, Vardis; Oustoglou, Erifili; Berrino, Franco; Vineis, Paolo; Mattiello, Amalia; Masala, Giovanna; Tumino, Rosario; Vrieling, Alina; van Gils, Carla H.; Peeters, Petra H.; Brustad, Magritt; Lund, Eiliv; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Rodriguez Suarez, Laudina; Molina, Esther; Dorronsoro, Miren; Sala, Nuria; Hallmans, Goran; Palmqvist, Richard; Roddam, Andrew; Key, Timothy J.; Khaw, Kay-Tee; Bingham, Sheila; Boffetta, Paolo; Autier, Philippe; Byrnes, Graham; Norat, Teresa; Riboli, Elio

    2009-01-01

    Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. It has been suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). However, current epidemiologic evidence from Eur

  5. Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells

    DEFF Research Database (Denmark)

    Jørgensen, Claus; Sherman, Andrew; Chen, Ginny I;

    2009-01-01

    Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how...... information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2......- and ephrin-B1-expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling...

  6. Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population

    Institute of Scientific and Technical Information of China (English)

    LI Wei-ju; ZHEN Yi-song; SUN Kai; XUE Hao; SONG Xiao-dong; WANG Yi-bo; FAN Xiao-han; HAN Yun-feng; HUI Ru-tai

    2008-01-01

    Background The ghrelin plays an important role in the regulation of food intake and energy homeostasis.Therefore,the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome.This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population.Methods Subjects consisted of 698 patients aged 41 to 80 years,diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria,and 762 age-and gender-matched controls.Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Odds ratios were estimated using a case-control study design by controlling confounding factors.Results The NA genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41,95%CI 1.03-1.94),increased waist circumference (OR 1.75,95%CI 1.26-2.42),and increased fast blood glucose (OR 1.49,95%CI 1.07-2.06) in women.The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37,95%CI 1.02-1.84).Conclusion The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

  7. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    Science.gov (United States)

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express.

  8. Nitrosamines as nicotinic receptor ligands.

    Science.gov (United States)

    Schuller, Hildegard M

    2007-05-30

    Nitrosamines are carcinogens formed in the mammalian organism from amine precursors contained in food, beverages, cosmetics and drugs. The potent carcinogen, NNK, and the weaker carcinogen, NNN, are nitrosamines formed from nicotine. Metabolites of the nitrosamines react with DNA to form adducts responsible for genotoxic effects. We have identified NNK as a high affinity agonist for the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) whereas NNN bound with high affinity to epibatidine-sensitive nAChRs. Diethylnitrosamine (DEN) bound to both receptors but with lower affinity. High levels of the alpha7nAChR were expressed in human small cell lung cancer (SCLC) cell lines and in hamster pulmonary neuroendocrine cells (PNECs), which serve as a model for the cell of origin of human SCLC. Exposure of SCLC or PNECs to NNK or nicotine increased expression of the alpha7nAChR and caused influx of Ca(2+), activation of PKC, Raf-1, ERK1/2, and c-myc, resulting in the stimulation of cell proliferation. Signaling via the alpha7nAChR was enhanced when cells were maintained in an environment of 10-15% CO(2) similar to that in the diseased lung. Hamsters with hyperoxia-induced pulmonary fibrosis developed neuroendocrine lung carcinomas similar to human SCLC when treated with NNK, DEN, or nicotine. The development of the NNK-induced tumors was prevented by green tea or theophylline. The beta-adrenergic receptor agonist, isoproterenol or theophylline blocked NNK-induced cell proliferation in vitro. NNK and nicotine-induced hyperactivity of the alpha7nAChR/RAF/ERK1/2 pathway thus appears to play a crucial role in the development of SCLC in smokers and could be targeted for cancer prevention.

  9. Androgen receptor (CAG)n polymorphisms and breast cancer risk in a Han Chinese population.

    Science.gov (United States)

    Dang, J; Peng, L; Zhong, H J; Huo, Z H

    2015-08-28

    The androgen receptor (AR) is involved in the differentiation and growth of breast cancer. Genetic markers in the AR gene have a plausible role in modulating the risk of breast cancer. In this study, we studied the association of breast cancer and the trinucleotide repeat polymorphism (CAG)n in exon 1 of the AR gene in 202 patients with breast cancer and 183 healthy controls from our hospital (Yinchuan, China). Repeat lengths were determined by fluorescent DNA fragment analysis using the ABI GeneScan software and DNA sequencing. We detected 17 short tandem repeat alleles in exon 1 in the Han population of Ningxia Province, China. The CAG repeat number ranged from 14 to 31 and the frequency ranged from 0.339 to 24.460%. Generally, (CAG)n repeat lengths 22 were classified as long (L). No association was found between breast cancer and the S/L (CAG) variants. However, the frequency of the (CAG)25 repeats in the breast cancer group was significantly higher than that in the control group (P = 0.033, odds ratio = 1.790, 95% confidence interval = 1.044-3.069). These findings indicate a role for AR gene (CAG)n variations in breast cancer and might be informative for future genetic or biological studies on breast cancer, although these findings need replication in other populations.

  10. Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population.

    Science.gov (United States)

    John, Esther M; Schwartz, Gary G; Koo, Jocelyn; Wang, Wei; Ingles, Sue A

    2007-12-15

    Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35-79 years from the San Francisco Bay Area of California (1995-2003). In-person interviews were obtained for 1,788 newly diagnosed cases and 2,129 controls. Skin pigmentation measurements were taken on the upper underarm (a sun-protected site that measures constitutive pigmentation) and on the forehead (a sun-exposed site) using reflectometry. Biospecimens were collected for a subset of the study population (814 cases, 910 controls). A high sun exposure index based on reflectometry was associated with reduced risk of advanced breast cancer among women with light constitutive skin pigmentation (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91). The association did not vary with VDR genotype. No associations were found for women with medium or dark pigmentation. Localized breast cancer was not associated with sun exposure or VDR genotype. This study supports the hypothesis that sunlight exposure reduces risk of advanced breast cancer among women with light skin pigmentation.

  11. Influence of drug treatment on glucocorticoid receptor levels in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    JI Hong; GUO Wei-zao; YAN Zhi-hong; LI Di; LU Cui-lian

    2010-01-01

    Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.Methods Eighty hospitalized patients (average age (59.0 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

  12. Noradrenalin and dopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex

    Directory of Open Access Journals (Sweden)

    Shinobu eNomura

    2014-08-01

    Full Text Available Noradrenergic fibers innervate the entire cerebral cortex, whereas the cortical distribution ofdopaminergic fibers is more restricted. However, the relative functional impact ofnoradrenalin and dopamine receptors in various cortical regions is largely unknown. Using aspecific genetic label, we first confirmed that noradrenergic fibers innervate the entire cortexwhereas dopaminergic fibers were present in all layers of restricted medial and lateral areasbut only in deep layers of other areas. Imaging of a genetically-encoded sensor revealed thatnoradrenalin and dopamine widely activate PKA in cortical pyramidal neurons of frontal,parietal and occipital regions with scarce dopaminergic fibers. Responses to noradrenalin hadhigher amplitude, velocity and occurred at more than 10 fold lower dose than those elicited bydopamine, whose amplitude and velocity increased along the antero-posterior axis. Thepharmacology of these responses was consistent with the involvement of Gs-coupled beta1adrenergic and D1/D5 dopaminergic receptors, but the inhibition of both noradrenalin anddopamine responses by beta adrenergic antagonists was suggestive of the existence of beta1-D1/D5 heteromeric receptors. Responses also involved Gi-coupled alpha2 adrenergic and D2-like dopaminergic receptors that markedly reduced their amplitude and velocity andcontributed to their cell-to-cell heterogeneity. Our results reveal that noradrenalin anddopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex withmoderate regional and laminar differences. These receptors can thus mediate widespreadeffects of both catecholamines, which are reportedly co-released by cortical noradrenergicfibers beyond the territory of dopaminergic fibers.

  13. Involvement of Fibroblast Growth Factor Receptor Genes in Benign Prostate Hyperplasia in a Korean Population

    Directory of Open Access Journals (Sweden)

    Hae Jeong Park

    2013-01-01

    Full Text Available Fibroblast growth factors (FGFs and their receptors (FGFRs have been implicated in prostate growth and are overexpressed in benign prostatic hyperplasia (BPH. In this study, we investigated whether single nucleotide polymorphisms (SNPs of the FGFR genes (FGFR1 and FGFR2 were associated with BPH and its clinical phenotypes in a population of Korean men. We genotyped four SNPs in the exons of FGFR1 and FGFR2 (rs13317 in FGFR1; rs755793, rs1047100, and rs3135831 in FGFR2 using direct sequencing in 218 BPH patients and 213 control subjects. No SNPs of FGFR1 or FGFR2 genes were associated with BPH. However, analysis according to clinical phenotypes showed that rs1047100 of FGFR2 was associated with prostate volume in BPH in the dominant model (GA/AA versus GG, P = 0.010. In addition, a significant association was observed between rs13317 of FGFR1 and international prostate symptom score (IPSS in the additive (TC versus CC versus TT, P = 0.0022 and dominant models (TC/CC versus TT, P = 0.005. Allele frequency analysis also showed significant association between rs13317 and IPSS (P = 0.005. These results suggested that FGFR genes could be related to progression of BPH.

  14. Distinct ErbB2 receptor populations differentially interact with beta1 integrin in breast cancer cell models

    Science.gov (United States)

    Toscani, Andrés Martín; Sampayo, Rocío G.; Barabas, Federico Martín; Fuentes, Federico; Simian, Marina

    2017-01-01

    ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation. We determined that beta1 integrin and ErbB2 colocalization is dependent on the expression level of both receptors exclusively in adherent cells. In suspension cells, lack of focal adhesions leave integrins free to diffuse on the plasma membrane and interact with ErbB2 even at low expression levels of both receptors. In adherent cells, high expression of beta1 integrin leaves unbound receptors outside focal complexes that diffuse within the plasma membrane and interact with ErbB2 membrane domains. Superresolution imaging showed the existence of two distinct populations of ErbB2: a major population located in large clusters and a minor population outside these structures. Upon ErbB2 overexpression, receptors outside large clusters can freely diffuse at the membrane and interact with integrins. These results reveal how expression levels of beta1 integrin and ErbB2 determine their frequency of colocalization and show that extracellular matrix proteins shape membrane clusters distribution, regulating ErbB2 and beta1 integrin activity in breast cancer cells. PMID:28306722

  15. An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Lynch, Joseph W

    2010-01-01

    for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain...

  16. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

    Energy Technology Data Exchange (ETDEWEB)

    Taouis, M.; Berlan, M.; Lafontan, M.

    1987-01-01

    The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with (/sup 3/H)yohimbine, whereas (/sup 3/H)clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, (/sup 3/H) clonidine and (/sup 3/H)yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of (/sup 3/H)clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations.

  17. Association pattern of interleukin-1 receptor-associated kinase-4 gene polymorphisms with allergic rhinitis in a Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    Full Text Available OBJECTIVE: Interleukin-1 receptor-associated kinase-4 (IRAK-4 encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4 gene are associated with allergic rhinitis (AR in the Han Chinese population. METHODS: A population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE. A total of 11 single nucleotide polymorphisms (SNPs in IRAK-4 were selected and individually genotyped. RESULTS: Significant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484 in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481. None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analysis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect. CONCLUSIONS: Our findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population.

  18. Vitamin-D receptor (VDR) gene polymorphisms (Taq-I & Apa-I) in Syrian healthy population.

    Science.gov (United States)

    Haddad, Shaden

    2014-12-01

    The vitamin D endocrine system regulates bone metabolism and calcium homeostasis as well as cellular proliferation and differentiation. Vitamin D receptor (VDR) mediates Vit-D activity, thus VDR gene polymorphisms may correlate with different diseases. This study aimed to determine the distribution of VDR gene (Taq-I and Apa-I) polymorphisms using a RFLP in unrelated normal healthy individuals of Syrian population. Allelic frequencies were 65% vs 35% and 66% vs 34% for T vs t and A vs a alleles, respectively. Genotype distribution was 36%, 58% and 6% for TT, Tt and tt and 42%, 47% and 10% for AA, Aa and aa, respectively. These results demonstrate that the frequency and distribution of the VDR polymorphisms in Syrian population are different from other populations worldwide.

  19. Is there evidence of selection in the dopamine receptorD4 gene in Australian invasive starling populations?

    Institute of Scientific and Technical Information of China (English)

    Lee Ann ROLLINS; Michael R WHITEHEAD; Andrew P WOOLNOUGH; Ron SINCLAIR; William B SHERWIN

    2015-01-01

    Although population genetic theory is largely based on the premise that loci under study are selectively neutral, it has been acknowledged that the study of DNA sequence data under the influence of selection can be useful. In some circumstances, these loci show increased population differentiation and gene diversity. Highly polymorphic loci may be especially useful when studying populations having low levels of diversity overall, such as is often the case with threatened or newly established inva-sive populations. Using common starlingsSturnus vulgaris sampled from invasive Australian populations, we investigated se-quence data of the dopamine receptor D4 gene (DRD4), a locus suspected to be under selection for novelty-seeking behaviour in a range of taxa including humans and passerine birds. We hypothesised that such behaviour may be advantageous when species encounter novel environments, such as during invasion. In addition to analyses to detect the presence of selection, we also esti-mated population differentiation and gene diversity usingDRD4 data and compared these estimates to those from microsatellite and mitochondrial DNA sequence data, using the same individuals. We found little evidence for selection onDRD4 in starlings. However, we did find elevated levels of within-population gene diversity when compared to microsatellites and mitochondrial DNA sequence, as well as a greater degree of population differentiation. We suggest that sequence data from putatively non- neutral loci are a useful addition to studies of invasive populations, where low genetic variability is expected [Current Zoology 61 (3): 505–519, 2015].

  20. 血管紧张素转化酶基因多态性与β受体阻滞剂治疗慢性心力衰竭患者预后的关系%Relationship between the polymorphism of angiotensin-converting enzyme and the prognosis of chronic heart failure patients treated with beta-adrenergic receptor blockers

    Institute of Scientific and Technical Information of China (English)

    郑茵; 方壮伟; 方团育; 吴智勇; 董吁钢; Dennis M. McNamara

    2011-01-01

    Objective: To evaluate the relationship between Angiotensin-Converting Enzyme ( ACE) polymor phisms and the prognosis of chronic heart failure( CHF) patients treatcd with β-blockers. Method: ACE I/D gene polymorphisms in 432 CHF- patients with systolic dysfunction (LVEF<0. 45) were detected by polymerase chain reaction (PCR) , and 26. 43±18. 19 months follow-up time were viewed to assess the end point of death in 432 CHD patients. At the same time, in diffcrent ACE I/D genotypes, relationships between the survival rate of CHF patients and β-blockers treatment were analyzed, too. Result: The survival of ACE D allele was significantly attenuated compared to Ⅰ allele (P=0. 027). In homozygous ACE DD patients, treatment withβ-blocker was associat ed with a significant improvement in survival rate(P=0. 003). However, In other patients treated with β-block ers , no obvious improvement of survival rate was viewcd in ACE Ⅱ、ID、DD genotype patients(P=0. 196). On the other hand, for patients without β-blockers treatment,there was a tendency of attenuation for survival rate in ACE DD not in ACE Ⅱ and ID patients, but with no statistical significance (P=0. 091). Conclusion : It shows that ACE DD genotype in CHF paticnts has significantly lower survival rate than in other genotype patients, which could be used as a predictive factor of prognosis for CHF patients, further,β-blocker therapy effects are related with ACE I/D gene polymorphisms, and β-blockers benefits ACE DD genotype patients most effcctively.%目的:探讨血管紧张素转化酶(ACE)基因多态性与β受体阻滞剂治疗心力衰竭患者预后的关系.方法:用聚合酶链式反应方法(PCR)检测432例收缩功能障碍性心力衰竭[左室射血分数(LVEF)<0.45]患者的ACE基因型,前瞻性随访所有患者(26.43±18.19)个月, 随访终点是死亡.分析不同ACE I/D基因分型中β受体阻滞剂治疗与慢性心力衰竭患者生存率的关系.结果:ACE D等位基因的生存率比Ⅰ等位基因明显降低(P=0.027);在ACE DD基因型中有β受体阻滞剂治疗组比无β受体阻滞剂治疗组的生存率明显增高(P=0.003);有β受体阻滞剂治疗组ACE II、ID、DD 3种基因型的生存率无差异(P=0.196);无β受体阻滞剂治疗组ACE DD基因型的生存率比II、ID有明显降低的趋势,但无显著性差异(P=0.091).结论:在慢性心力衰竭患者中,ACE DD基因型患者的生存率明显降低,β受体阻滞剂治疗效果与ACE I/D基因多态性有相关性,ACE DD基因型获益更大.

  1. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

  2. Downregulation of protease-activated receptor-1 in human lung fibroblasts is specifically mediated by the prostaglandin E receptor EP2 through cAMP elevation and protein kinase A.

    Science.gov (United States)

    Sokolova, Elena; Hartig, Roland; Reiser, Georg

    2008-07-01

    Many cellular functions of lung fibroblasts are controlled by protease-activated receptors (PARs). In fibrotic diseases, PAR-1 plays a major role in controlling fibroproliferative and inflammatory responses. Therefore, in these diseases, regulation of PAR-1 expression plays an important role. Using the selective prostaglandin EP2 receptor agonist butaprost and cAMP-elevating agents, we show here that prostaglandin (PG)E(2), via the prostanoid receptor EP2 and subsequent cAMP elevation, downregulates mRNA and protein levels of PAR-1 in human lung fibroblasts. Under these conditions, the functional response of PAR-1 in fibroblasts is reduced. These effects are specific for PGE(2). Activation of other receptors coupled to cAMP elevation, such as beta-adrenergic and adenosine receptors, does not reproduce the effects of PGE(2). PGE(2)-mediated downregulation of PAR-1 depends mainly on protein kinase A activity, but does not depend on another cAMP effector, the exchange protein activated by cAMP. PGE(2)-induced reduction of PAR-1 level is not due to a decrease of PAR-1 mRNA stability, but rather to transcriptional regulation. The present results provide further insights into the therapeutic potential of PGE(2) to specifically control fibroblast function in fibrotic diseases.

  3. Diversity of killer cell immunoglobulin-like receptor genes in Indonesian populations of Sumatra, Sulawesi and Moluccas Islands.

    Science.gov (United States)

    Velickovic, M; Velickovic, Z; Panigoro, R; Dunckley, H

    2010-10-01

    Killer immunoglobulin-like receptors (KIRs) regulate the activity of natural killer and T cells through interaction with specific human leukocyte antigen (HLA) molecules on target cells. Like HLA class I genes that are characterised by extreme allelic polymorphism, KIR genes are diverse and vary in both gene content and allelic polymorphism. Population studies conducted over the last several years have showed that KIR gene frequencies (GF) and genotype content vary among different ethnic groups, indicating the extent of KIR diversity. Some studies have also shown the effect of the presence or absence of specific KIR genes in human disease. We have recently reported the distribution of KIR genes in populations from Java (Central Javanese and the Sundanese of West Java), East Timor (Timorese), Kalimantan provinces of Indonesian Borneo (Dayaks) and Irian Jaya (Western half of the island of New Guinea; Melanese). We here extend analysis of the KIR genes in populations from North Sulawesi (Minahasans), West Sumatra (Minangs) and Moluccas Islands. All 16 KIR genes were observed in all three populations. Variation in GF between populations was observed, except for the KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 genes, which were present in every individual tested. When comparing KIR GF between populations, both principal component analysis and phylogenetic tree analyses showed a close relationship between Minahasan and Moluccan populations that are clustered with Timorese in the same clade. The Minang tribe lies between the Javanese/Kalimantan and the Timorese/Minahasan/Moluccan clades, whereas Irianese show the greatest genetic distances from other Indonesian populations. The results correspond well with the history of migration in Indonesia and will contribute to the understanding of the genetic as well as the geographic history of the region.

  4. The regularity of sustained firing reveals two populations of slowly adapting touch receptors in mouse hairy skin.

    Science.gov (United States)

    Wellnitz, Scott A; Lesniak, Daine R; Gerling, Gregory J; Lumpkin, Ellen A

    2010-06-01

    Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell-neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin-nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 +/- 0.09) and SAII responses (0.21 +/- 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein-expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin-nerve recordings for genetic dissection of touch receptor mechanisms.

  5. A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

    NARCIS (Netherlands)

    Conzelmann, S; Levai, O; Bode, B; Eisel, U; Raming, K; Breer, H; Strotmann, J

    2000-01-01

    Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a different

  6. β3-Adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population

    NARCIS (Netherlands)

    Oeveren van-Dybicz, A.M.; Vonkeman, H.E.; Bon, M.A.M.; Bergh, van den F.A.J.T.M.; Vermes, I.

    2008-01-01

    Aim: The β3-adrenergic receptor (β3-AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the β3-AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes me

  7. Beta adrenoreceptors in the rabbit bladder detrusor muscle

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, G.F.; Marks, B.H.

    1984-02-01

    This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.

  8. Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro.

    Science.gov (United States)

    Haas, H L; Rose, G M

    1987-07-22

    The actions of noradrenaline and the beta-adrenergic agonist, isoproterenol, were studied on the dentate gyrus in hippocampal slices from rats using extra- and intracellular recording. These agents facilitated field EPSPs (excitatory postsynaptic potentials) and population spikes evoked by perforant path stimulation. Intracellular recording revealed an attenuation of the long lasting afterhyperpolarization (AHP) and the accommodation of cell discharge in response to depolarizing current injection. It is suggested that beta-receptor activation blocks a calcium-dependent potassium current.

  9. The effect of chronic in vivo infusion of forskolin on noradrenergic receptor sensitivity.

    Science.gov (United States)

    Suzdak, P D; Browne, R G

    1985-01-01

    Forskolin, a diterpene isolated from the plant Coleus forskolii, activates the catalytic subunit of adenylate cyclase, resulting in a hormone receptor-independent increase in the intracellular production of cyclic AMP. This study was undertaken to assess the effect of chronic in vivo infusion of forskolin on noradrenergic neuronal activity. Forskolin was infused into the right lateral ventricle of male Sprague Dawley rats via Alzet osmotic minipumps (model 2001) for 7 days. Chronic infusion of forskolin resulted in a decrease in norepinephrine-stimulated cyclic AMP accumulation in the limbic forebrain. Chronic infusion of forskolin also resulted in a decrease in the Bmax for 3H-dihydroalprenolol (3H-DHA) binding to beta-adrenergic receptors in the cerebral cortex and hippocampus, with no apparent change in the Kd values. These data suggest the possibility of a novel therapeutic approach to modulating receptor sensitivity, and that chronic infusion of forskolin may be a useful model for studying the role of cyclic AMP in the control of neuronal activity.

  10. Prevalence of estrogen receptor alpha PvuII and XbaI polymorphism in population of Polish postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Jozef Haczynski

    2008-01-01

    Full Text Available Numerous data indicate that polymorphism of estrogen receptor alpha (ERalpha may predict lipid levels, lipid response to hormone replacement therapy (HRT, myocardial infarction risk, bone fracture risk, bone mineral density (BMD and changes in BMD over time. In this study we aimed to evaluate distribution of ERalpha PvuII and XbaI genotypes in population of Polish postmenopausal women qualified to different protocols of HRT. Subject of the study were 64 consecutive postmenopausal women aged from 45 to 65 years (mean 56.6 assigned to HRT. ERalpha PvuII and XbaI polymorphism was determined by PCR-restriction fragment length polymorphism (RFLP. The absence of PvuII and XbaI restriction sites were indicated by "P" and "X" and presence by "p" and "x", respectively. PvuII genotype was distributed as follows: PP 17.2% (n=11, Pp 50% (n=32, pp 32.83% (n=21. Frequency of XbaI genotype was: XX 6.25% (n=4, Xx 34.4% (n=22, xx 59.4% (n=38. Four haplotypes with following frequencies were recognized: PX 17.3%, px 47.4%, Px 24.4% and pX 10.9%. Prevalence of estrogen receptor alpha PvuII and XbaI polymorphisms in Polish women is similar to previously studied population.

  11. Control of yeast mating signal transduction by a mammalian. beta. sub 2 -adrenergic receptor and G sub s. alpha. subunit

    Energy Technology Data Exchange (ETDEWEB)

    King, K.; Caron, M.G.; Lefkowitz, R.J. (Duke Univ. Medical Center, Durham, NC (USA)); Dohlman, H.G.; Thorner, J. (Univ. of California, Berkeley (USA))

    1990-10-05

    To facilitate functional and mechanistic studies of receptor-G protein interactions by expression of the human {beta}{sub 2}-adrenergic receptor (h{beta}-AR) has been expressed in Saccharomyces cerevisiae. This was achieved by placing a modified h{beta}-AR gene under control of the galactose-inducible GAL1 promoter. After induction by galactose, functional h{beta}-AR was expressed at a concentration several hundred times as great as that found in any human tissue. As determined from competitive ligand binding experiments, h{beta}-AR expressed in yeast displayed characteristic affinities, specificity, and stereoselectivity. Partial activation of the yeast pheromone response pathway by {beta}-adrenergic receptor agonists was achieved in cells coexpressing h{beta}-AR and a mammalian G protein (G{sub s}) {alpha} subunit - demonstrating that these components can couple to each other and to downstream effectors when expressed in yeast. This in vivo reconstitution system provides a new approach for examining ligand binding and G protein coupling to cell surface receptors.

  12. Reproductive pattern in agrarian and immigrant receptor populations: a survey of El Ejido (SE Spain).

    Science.gov (United States)

    Alonso, Verónica; Luna, Francisco

    2005-06-01

    This paper deals with the fertility pattern of the El Ejido population, an agricultural Spanish community characterised by the rapid development of its modern agrarian economy. Consequently, the arrival of immigrants has sharply increased throughout the second half of the twentieth century, with important demographic consequences as well as reproductive changes. The analyses of the age-specific fertility rate (fx) and the total fertility rate (TFR) were used in order to describe the reproductive pattern of this population in 2000. The main characteristics were the following: a) Regarding the temporal change, an important decrease of fx has been observed in all age groups for the last twenty years, as a consequence of progressive birth control. However, the reproductive pattern has kept almost invariable and has been characterised by a maximum fertility at age group of 25-29 years old. b) Regarding the general Spanish fertility, the comparison of fx in both populations suggests a younger maternity in the agricultural population than in the national, the maximum fertility delayed to the 30-34 age group. c) Moreover, the El Ejido population showed a clear higher offspring per woman (TFR = 1.42) than the national (TFR = 1.24), according to the agrarian character of the El Ejido population. d) Finally, this greater reproductive level of El Ejido is also due to the arrival of women at fertile age, who come mainly from Africa, and above all from Morocco.

  13. The octopamine receptor Octβ2R regulates ovulation in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Junghwa Lim

    Full Text Available Oviposition is induced upon mating in most insects. Ovulation is a primary step in oviposition, representing an important target to control insect pests and vectors, but limited information is available on the underlying mechanism. Here we report that the beta adrenergic-like octopamine receptor Octβ2R serves as a key signaling molecule for ovulation and recruits protein kinase A and Ca(2+/calmodulin-sensitive kinase II as downstream effectors for this activity. We found that the octβ2r homozygous mutant females are sterile. They displayed normal courtship, copulation, sperm storage and post-mating rejection behavior but were unable to lay eggs. We have previously shown that octopamine neurons in the abdominal ganglion innervate the oviduct epithelium. Consistently, restored expression of Octβ2R in oviduct epithelial cells was sufficient to reinstate ovulation and full fecundity in the octβ2r mutant females, demonstrating that the oviduct epithelium is a major site of Octβ2R's function in oviposition. We also found that overexpression of the protein kinase A catalytic subunit or Ca(2+/calmodulin-sensitive protein kinase II led to partial rescue of octβ2r's sterility. This suggests that Octβ2R activates cAMP as well as additional effectors including Ca(2+/calmodulin-sensitive protein kinase II for oviposition. All three known beta adrenergic-like octopamine receptors stimulate cAMP production in vitro. Octβ1R, when ectopically expressed in the octβ2r's oviduct epithelium, fully reinstated ovulation and fecundity. Ectopically expressed Octβ3R, on the other hand, partly restored ovulation and fecundity while OAMB-K3 and OAMB-AS that increase Ca(2+ levels yielded partial rescue of ovulation but not fecundity deficit. These observations suggest that Octβ2R have distinct signaling capacities in vivo and activate multiple signaling pathways to induce egg laying. The findings reported here narrow the knowledge gap and offer insight into novel

  14. Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia: A comparison of genetic variants in two independent patient populations

    Directory of Open Access Journals (Sweden)

    Svetlana A Ivanova

    2016-04-01

    Full Text Available Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia. Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431 and a long-stay population from the Netherlands (N = 168. These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared. Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423 was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant. Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia.

  15. Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population.

    Science.gov (United States)

    Ikeda, Masashi; Iwata, Nakao; Kitajima, Tsuyoshi; Suzuki, Tatsuyo; Yamanouchi, Yoshio; Kinoshita, Yoko; Ozaki, Norio

    2006-04-01

    Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology of schizophrenia. The 5-HT7 receptor is considered to be a possible schizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT7 receptor gene (HTR7) and selected four 'haplotype-tagging (ht) SNPs'. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japanese schizophrenia patients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated with schizophrenia. A promoter SNP (SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function of HTR7, our results support the supposition that HTR7 is a susceptibility gene for schizophrenia in this ethnic group.

  16. Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population.

    Science.gov (United States)

    Liu, Xiaoxi; Kawamura, Yoshiya; Shimada, Takafumi; Otowa, Takeshi; Koishi, Shinko; Sugiyama, Toshiro; Nishida, Hisami; Hashimoto, Ohiko; Nakagami, Ryoichi; Tochigi, Mamoru; Umekage, Tadashi; Kano, Yukiko; Miyagawa, Taku; Kato, Nobumasa; Tokunaga, Katsushi; Sasaki, Tsukasa

    2010-03-01

    The oxytocin receptor (OXTR) gene, which is located on chromosome 3p25.3, has been implicated as a candidate gene for susceptibility of autism spectrum disorder (ASD). Positive associations between OXTR and ASD have been reported in earlier studies. However, the results were inconsistent and demand further studies. In this study, we investigated the associations between OXTR and ASD in a Japanese population by analyzing 11 single-nucleotide polymorphisms (SNPs) using both family-based association test (FBAT) and population-based case-control test. No significant signal was detected in the FBAT test. However, significant differences were observed in allelic frequencies of four SNPs, including rs2254298 between patients and controls. The risk allele of rs2254298 was 'A', which was consistent with the previous study in Chinese, and not with the observations in Caucasian. The difference in the risk allele of this SNP in previous studies might be attributable to an ethnic difference in the linkage disequilibrium structure between the Asians and Caucasians. In addition, haplotype analysis exhibits a significant association between a five-SNP haplotype and ASD, including rs22542898. In conclusion, our study might support that OXTR has a significant role in conferring the risk of ASD in the Japanese population.

  17. Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity.

    Directory of Open Access Journals (Sweden)

    Anette P Gjesing

    Full Text Available BACKGROUND: The growth hormone secretagogue receptor (GHSR is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p0.05 could be shown. CONCLUSIONS/SIGNIFICANCE: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.

  18. The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.

    Science.gov (United States)

    Wang, Li; Liu, Jun; Saha, Pradip; Huang, Jiansheng; Chan, Lawrence; Spiegelman, Bruce; Moore, David D

    2005-10-01

    Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.

  19. Effect of chronic metoprolol and coronary occlusion (CO) on cardiac beta receptor density in cats

    Energy Technology Data Exchange (ETDEWEB)

    Lathers, C.M.; Spivey, W.H.; Levin, R.M.

    1986-03-05

    The effect of metoprolol (M) on beta receptor density (BRD) was examined. M (5 mg/kg, p.o., b.i.d.) was given for 2 and 8 wks prior to CO of the left anterior descending artery (LAD) at its origin. BRD, determined by binding of /sup 3/H-dihydroalprenol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal LAD distribution, LV = 2 distal LAD distribution, LV3 = posterior left ventricle, RV = right ventricle, and S = septum. A 2 factor ANOVA followed by simple effect and Newman-Keuls post hoc tests revealed that M produced no effect in BRD in LA, RA, LV2, or S. M increased BRD in LV1, LV3, and RV after 2 wk when compared to no M. In addition, BRD in LV3 and RV were also greater at 2 wk than after 8 wk M. The data indicate that there are regional differences in the beta adrenergic receptor densities among the areas of the heart and within the left ventricle. Chronic dosing with M produced increased BRD in only some of the areas of the heart. These differences may be related to functional differences in the various areas of the heart after CO.

  20. The effects of dietary fish oil on cell populations, cytokines, chemokines and chemokine receptors in healthy mice and mice with endotoxin-induced peritonitis

    OpenAIRE

    Hildur Hrönn Arnardóttir 1981

    2011-01-01

    Fish oil, rich in n-3 polyunsaturated fatty acids, has immunomodulatory properties and may have beneficial effects in several immune related disorders, including sepsis. Chemokines and chemokine receptors play a key role in the recruitment of specific populations of immune cells to the sites of infection or inflammation. The results from the Ph.D. project show that dietary fish oil decreased the proportion of classical monocytes(expressing the chemokine receptor CCR2) in blood from healthy mi...

  1. Association between Alcoholism and the Genetic Polymorphisms of the GABAA Receptor Genes on Chromosome 5q33-34 in Korean Population

    OpenAIRE

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-01-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute...

  2. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  3. Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity

    DEFF Research Database (Denmark)

    Gjesing, Anette P.; Larsen, Lesli Hingstrup; Torekov, Signe Sørensen;

    2010-01-01

    BACKGROUND: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight...... transcriptional activity (pintroduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non......-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown. CONCLUSIONS/SIGNIFICANCE: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related...

  4. Polymorphic CAG and GGC repeat lengths in the androgen receptor gene and prostate cancer risk: analysis of a Brazilian population.

    Science.gov (United States)

    Silva Neto, Brasil; Koff, Walter J; Biolchi, Vanderlei; Brenner, Cleber; Biolo, Karlo D; Spritzer, Poli Mara; Brum, Ilma S

    2008-02-01

    Variations in transcriptional activity of the androgen receptor (AR) are related to polymorphic CAG and GGC repeats in exon 1 of the AR gene. We investigated the association between CAG and GGC repeat length and the risk of prostate cancer in a case-control study from a Brazilian population. We evaluated 49 patients and 51 healthy controls. DNA was extracted from peripheral leukocytes and the AR gene was analyzed by fragment analysis (GeneMapper software, Applied Biosystems, Foster City, California, USA). CAG and GGC mean lengths were not different between cases and controls. The risk for prostate cancer was higher for CAG repeats repeat lengths (CAG + GGC) repeats ( 17) were not associated with risk for prostate cancer (OR = 1.13 [95% CI 0.47-2.75]). In conclusion, fewer number of CAG repeats and total repeats (CAG + GGC) in the AR gene may be associated with increased risk for prostate cancer.

  5. Prognostic significance of fibroblast growth factor receptor 4 polymorphisms on biochemical recurrence after radical prostatectomy in a Chinese population

    Science.gov (United States)

    Chen, Luyao; Lei, Zhengwei; Ma, Xin; Huang, Qingbo; Zhang, Xu; Zhang, Yong; Hao, Peng; Yang, Minggang; Zhao, Xuetao; Chen, Jun; Liu, Gongxue; Zheng, Tao

    2016-01-01

    Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane receptor with ligand-induced tyrosine kinase activity and is involved in various biological and pathological processes. Several polymorphisms of FGFR4 are associated with the incidence and mortality of numerous cancers, including prostate cancer. In this study, we investigated whether the polymorphisms of FGFR4 influence the biochemical recurrence of prostate cancer in Chinese men after radical prostatectomy. Three common polymorphisms (rs1966265, rs2011077, and rs351855) of FGFR4 were genotyped from 346 patients with prostate cancer by using the Sequenom MassARRAY system. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis. Results showed biochemical recurrence (BCR) free survival was significantly affected by the genotypes of rs351855 but not influenced by rs1966265 and rs2011077. After adjusting for other variables in multivariable analysis, patients with rs351855 AA/AG genotypes showed significantly worse BCR-free survival than those with the GG genotype (HR = 1.873; 95% CI, 1.209–2.901; P = 0.005). Hence, FGFR4 rs351855 could be a novel independent prognostic factor of BCR after radical prostatectomy in the Chinese population. This functional polymorphism may also provide a basis for surveillance programs. Additional large-scale studies must be performed to validate the significance of this polymorphism in prostate cancer. PMID:27640814

  6. Association between Opioid Receptor mu 1 (OPRM1 Gene Polymorphisms and Tobacco and Alcohol Consumption in a Spanish Population

    Directory of Open Access Journals (Sweden)

    Francesc Francès

    2015-04-01

    Full Text Available Evidence gained from animals and humans suggests that the encephalic opioid system might be involved in the development of drug addiction through its role in reward. Our aim is to assess the influence of genetic variations in the opioid receptor mu 1 on alcohol and tobacco consumption in a Spanish population. 763 unrelated individuals (465 women, 298 men aged 18-85 years were recruited between October 2011 and April 2012. Participants were requested to answer a 35-item questionnaire on tobacco and alcohol consumption, as well as to complete the AUDIT and Fagerström tests. Individuals were genotyped for three polymorphisms in the opioid receptor mu 1 (OPRM1 gene, using a TaqMan® protocol. In males, the rs10485057 polymorphism was associated with total pure ethanol intake and with the risk of being an alcohol consumer. Also, this polymorphism was significantly associated with higher Fagerström scores. Rs1799971 had a different influence on adaptive and maladaptive patterns of alcohol use. Despite the limited sample size, our study might enrich current knowledge on patterns of alcohol use, because it encompasses both extreme and adaptive phenotypes, providing thus a wider perspective on this subject.

  7. Mutation analysis underlying the downregulation of the thyroid hormone receptor β1 gene in the Chinese breast cancer population

    Directory of Open Access Journals (Sweden)

    Ling YQ

    2015-10-01

    Full Text Available Yaqin Ling,1 Xiaoling Ling,2 Lu Fan,1 Yong Wang,3,* Qing Li1,* 1Department of Pathophysiology, College of Basic Medical, Lanzhou University, 2Medical Oncology, Lanzhou University First Hospital, 3Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command of PLA, Lanzhou, Gansu Province, People’s Republic of China *These authors contributed equally to this work Purpose: There are a growing number of reports suggesting that the aberrant expression and mutation of the thyroid hormone receptor β1 (TRβ1 gene is associated with the development of human neoplasms. However, its exact role in the pathogenesis of breast cancer remains elusive. In the present study, we analyzed the mRNA expression and mutations of the TRβ1 gene in the Chinese breast cancer population.Methods: The expression of TRβ1 mRNA was examined by real-time quantitative reverse transcription polymerase chain reaction, and mutations in the TRβ1 gene in the hotspot region that spans exons 7–10 were analyzed by polymerase chain reaction single-strand conformation polymorphism and automated DNA sequencing.Results: TRβ1 mRNA expression was significantly reduced in all 105 breast cancer specimens examined. A total of 20 samples showed truncating mutations within the exons 7–10 of the TRβ1 gene, where eight cases harbored a frame shift mutation (five cases of c.850insA in exon 7 and three cases c.1028delA in exon 8, whereas missense mutations were observed in 12 breast cancer cases. The 20 cases with mutation in the TRβ1 gene showed a reduction in TRβ1 mRNA expression compared with that observed in matched normal tissues. The mutation was also correlated with menopausal stage and estrogen receptor status.Conclusion: The findings of the present study suggest that the aberrant expression and mutations of the TRβ1 gene are associated with the development of breast cancer and that the ­mutations in the TRβ1 gene partly serve as the underlying

  8. Potentially functional polymorphism in IL-23 receptor and risk of acute myeloid leukemia in a Chinese population.

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    Xifeng Qian

    Full Text Available The interleukin-23 (IL-23 and its receptor (IL-23R mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR = 1.28, 95% confidence interval (CI = 1.01-1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01-1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

  9. Investigation of Chemokine Receptor CCR2V64Il Gene Polymorphism and Migraine without Aura in the Iranian Population

    Directory of Open Access Journals (Sweden)

    Alireza Zandifar

    2013-01-01

    Full Text Available Background and Objectives. Migraine is a multifactorial common neurovascular disease with a polygenic inheritance. Inflammation plays an important part in migraine pathophysiology. C-C chemokine receptor 2 (CCR2 is an important chemokine for monocyte aggregation and transendothelial monocyte migration. The aim of our study was to investigate the association of migraine with CCR2V64Il polymorphism in the Iranian population. Methods. We assessed 103 patients with newly diagnosed migraine and 100 healthy subjects. Genomic DNA samples were extracted from peripheral blood and genotypes of CCR2V64Il gene polymorphism were determined. For measuring the severity of headache, every patient filled out the MIGSEV questionnaire. Results. There were no significant differences in the distribution of both 64Il allele and heterozygote (GA genotype of CCR2 gene polymorphism (P=0.396; OR=0.92, 95% CI = 0.50–1.67 and P=0.388; OR=0.91, 95% CI = 0.47–1.73, resp. between case and control groups. There was no significant difference of alleles frequency between three grades of MIGSEV (P=0.922. Conclusions. In conclusion our results revealed no association between CCR2V64Il polymorphism and susceptibility to migraine and also headache severity in the Iranian population.

  10. Toll-like receptor 9 is correlated to disease activity in Chinese systemic lupus erythematosus population

    Institute of Scientific and Technical Information of China (English)

    MU Rong; SUN Xiao-yun; Lik Thai Lim; XU Chuan-hui; DAI Chen-xian; SU Yin; JIA Ru-lin; LI Zhan-guo

    2012-01-01

    Background Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models.Its pathogenic role in human SLE,however,was poorly elucidated.This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.Methods mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR).IFN-α expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA).Results TLR9 expression was significantly higher in SLE patients than that in health controls (P=-0.011).SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P=0.001).TLR9 expression was positively correlated with fever (P=0.017),alopecia (P=0.046),safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (rs=0.385,P=0.003),and the level of IRF5 (rs=0.35,P=0.027) and IFN-α (rs=0.627,P=0.001) in SLE patients.Conclusion TLR9 is associated with SLE disease activity and might be involved in the IFN-α pathway of SLE.

  11. CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice.

    Science.gov (United States)

    Orr, Jeb S; Kennedy, Arion J; Hill, Andrea A; Anderson-Baucum, Emily K; Hubler, Merla J; Hasty, Alyssa H

    2016-09-01

    The mechanism by which macrophages and other immune cells accumulate in adipose tissue (AT) has been an area of intense investigation over the past decade. Several different chemokines and their cognate receptors have been studied for their role as chemoattractants in promoting recruitment of immune cells to AT However, it is also possible that chemoattractants known to promote clearance of immune cells from tissues to regional lymph nodes might be a critical component to overall AT immune homeostasis. In this study, we evaluated whether CCR7 influences AT macrophage (ATM) or T-cell (ATT) accumulation. CCR7(-/-) and littermate wild-type (WT) mice were placed on low-fat diet (LFD) or high-fat diet (HFD) for 16 weeks. CCR7 deficiency did not impact HFD-induced weight gain, hepatic steatosis, or glucose intolerance. Although lean CCR7(-/-) mice had an increased proportion of alternatively activated ATMs, there were no differences in ATM accumulation or polarization between HFD-fed CCR7(-/-) mice and their WT counterparts. However, CCR7 deficiency did lead to the preferential accumulation of CD8(+) ATT cells, which was further exacerbated by HFD feeding. Finally, expression of inflammatory cytokines/chemokines, such as Tnf, Il6, Il1β, Ccl2, and Ccl3, was equally elevated in AT by HFD feeding in CCR7(-/-) and WT mice, while Ifng and Il18 were elevated by HFD feeding in CCR7(-/-) but not in WT mice. Together, these data suggest that CCR7 plays a role in CD8(+)ATT cell egress, but does not influence ATM accumulation or the metabolic impact of diet-induced obesity.

  12. Altered adrenergic response and specificity of the receptors in rat ascites hepatoma AH130.

    Science.gov (United States)

    Sanae, F; Miyamoto, K; Koshiura, R

    1989-11-15

    Adenylate cyclase activation through adrenergic receptors in rat ascites hepatoma (AH) 130 cells in response to adrenergic drugs was studied, and receptor binding and displacement were compared with those of normal rat hepatocytes. Epinephrine (Epi) and norepinephrine (NE) activated AH130 adenylate cyclase about half as much as isoproterenol (IPN) but equaled IPN after treatment with the alpha-antagonist phentolamine or islet-activating protein (IAP). The three catecholamines in hepatocytes were similar regardless of phentolamine or IAP. These catecholamines activated adenylate cyclase in order of IPN greater than NE greater than Epi in AH130 cells but IPN greater than Epi greater than NE in hepatocytes. We then used the alpha 1-selective ligand [3H]prazosin, the alpha 2-selective ligand [3H]clonidine, and the beta-ligand [125I]iodocyanopindolol [( 125I]ICYP), and found that AH130 cells had few prazosin-binding sites, about eight times as many clonidine-binding sites with high affinity, and many more ICYP-binding sites than in hepatocytes. The dissociation constant (Ki) of the beta 1-selective drug metoprolol by Hofstee plots for AH130 cells was lower than that for hepatocytes. The inhibition of specific ICYP binding by the beta 2-selective agonist salbutamol for AH130 cells gave only one Ki value which was much higher than both high and low Ki values of the drug for hepatocytes. These findings indicate that the alpha- and beta-adrenergic receptors in hepatocytes are predominantly alpha 1-type and beta 2-type, but that those in AH130 cells are predominantly alpha 2-type and beta 1-type, and the low adrenergic response of AH130 cells is due to the dominant appearance of alpha 2-adrenergic receptors, linked with the inhibitory guanine-nucleotide binding regulatory protein, instead of alpha 1-adrenergic receptors, and beta 1-adrenergic receptors with low affinity for the hormone.

  13. Lack of associations between serum leptin, a polymorphism in the gene for the beta(3)-adrenergic receptor and glucose tolerance in the Dutch population.

    NARCIS (Netherlands)

    Janssen, JAMJL; Koper, JW; Stolk, RP; Englaro, P; Uitterlinden, AG; Huang, Q; van Leeuwen, JPTM; Blum, WF; Attanasio, AMF; Pols, HAP; Grobbee, DE; de Jong, FH; Lamberts, SWJ

    1998-01-01

    BACKGROUND The associations between leptin levels and the prevalence of a polymorphism in the beta(3)-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS

  14. Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population

    Science.gov (United States)

    Figuera, Luis E.; Flores-Ramos, Liliana Gómez; Puebla-Pérez, Ana María; Zúñiga-González, Guillermo Moisés

    2015-01-01

    Introduction The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland. Material and methods We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC). Results The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1–2.6, p = 0.009, for the T1/T2–T2/T2 genotypes. The association was also evident when the distributions of the T1/T2–T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03–3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27–3.067, p = 0.002). Conclusions The T1/T2–T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population. PMID:26170848

  15. Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

    Science.gov (United States)

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-06-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

  16. Beta-receptor activation increases sodium current in guinea pig heart

    Institute of Scientific and Technical Information of China (English)

    Hong-wei WANG; Zhi-fang YANG; Yin ZHANG; Jian-min YANG; Yuan-mou LIU; Ci-zhen LI

    2009-01-01

    Aim: To study the influence of β-receptor activation on sodium channel current and the physiological significance of increased sodium current with regard to the increased cardiac output caused by sympathetic excitation.Methods: Multiple experimental approaches, including ECG, action potential recording with conventional microelectrodes, whole-cell current measurements, single-channel recordings, and pumping-force measurements, were applied to guinea pig hearts and isolated ventricular myocytes.Results: Isoprenaline was found to dose-dependently shorten QRS waves, increase the amplitude and the Vmaxof action potentials, aug-ment the fast sodium current, and increase the occurrence frequencies and open time constants of the long-open and burst modes of the sodium channel. Increased levels of membrane-permeable cAMP have similar effects. In the presence of a calcium channel blocker, TTX reversed the increased pumping force produced by isoprenaline.Conclusion: Beta-adrenergic modulation increases the inward sodium current and accelerates the conduction velocity within the ventri-cles by changing the sodium channel modes, which might both be conducive to the synchronous contraction of the heart and enhance its pumping function.

  17. Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations

    Science.gov (United States)

    Liang, Hui-ling; Ma, Shu-juan; Tan, Hong-zhuan

    2017-01-01

    Abstract Background: Recently, a growing number of studies show that the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms may play a role in the systemic lupus erythematosus (SLE) susceptibility. Nonetheless, the results were inconsistent. Thus, a meta-analysis was carried out by integrating multiple research to clarify the association between KIR polymorphisms and SLE susceptibility. Methods: The Web of Science, Embase (Ovid), PubMed, Elsevier Science Direct, the Chinese Biomedical Database and CNKI, Wanfang databases (last search was updated on May 15, 2016) were systematically searched to select studies on addressing the association between the KIR polymorphisms and susceptibility to SLE in populations. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated. Results: A total of 10 published case-control studies involving 1450 SLE patients and 1758 controls were available for this meta-analysis. Results suggested that KIR2DL1 might be a risk factor for SLE (OR 2DL1 =1.047, 95% CI=1.011–1.083) in all subjects. The KIR2DL3, KIR2DL5 were identified as protective factors for SLE in Asian populations (OR2DL3= 0.215, 95% CI = 0.077–0.598; OR2DL5 = 0.588, 95% CI = 0.393–0.881), but not in Caucasians. Conclusions: The meta-analysis results suggested that 2DL1 might be a potential risk factor and 2DL3, 2DL5 might be protective factors for SLE in Asians but not in Caucasians. PMID:28272205

  18. Association Study of Vitamin D Receptor (VDR) - Related Genetic Polymorphisms and their Haplotypes with Chronic Periodontitis in Colombian Population

    Science.gov (United States)

    Isaza-Guzmán, Diana María; Pineda-Trujillo, Nicolás

    2017-01-01

    Introduction There is strong evidence that both genetic and environmental factors may affect the periodontal clinical status. However, epidemiological evidence on the association between Vitamin D Receptor (VDR) polymorphisms and Chronic Periodontitis (CP) has been inconsistent. Aim The focus of this study was to identify if a possible association between VDR Single-Nucleotide Polymorphisms (SNPs) may be implicated in the aetiopathogenesis of CP in Colombian population. Materials and Methods One hundred and ten CP patients and 50 Healthy Controls (HC) were recruited. Periodontal status was assessed based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify the VDR rs7975232, rs1544410, rs2228570, and rs731236 SNPs from saliva samples. Odds Ratios (ORs) along with their 95% Confidence Intervals (CIs) were computed to compare the distribution of genotypes/alleles between HC and CP patients, alongside with analysis of Linkage Disequilibrium (LD) and haplotype associations between SNPs. Also, an analysis of the interaction between genetic findings and those significant demographic factors was performed for all SNPs. Results There was no association neither between the different genotypes/allele frequencies nor haplotypes and CP. Similarly, no significant differences in extent or severity amongst genotype/allele groups were observed. Even so, interaction analysis revealed significant synergistic interactions between each SNP and age associated with the disease status. Conclusion Although these results do not support that VDR SNPs could be identified as independent risk predictor variables for CP in the Colombian population, synergistic biological interactive effects of all these SNPs related to age might play a significant role in the pathogenic pathways of CP. PMID:28384983

  19. Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

    Directory of Open Access Journals (Sweden)

    Chun Wang

    Full Text Available Low density lipoprotein receptor-related protein 2 gene (LRP2 is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH(2D(3. In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591. BMD values at the lumbar spine 1-4 (L1-4 and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population.

  20. Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: A population-based study

    Energy Technology Data Exchange (ETDEWEB)

    `t Hart, L.M.; Maassen, J.A. [Leiden Univ. (Netherlands); Does, F.E.E. van der [Free Univ., Amsterdam (Netherlands)] [and others

    1996-11-01

    One of the characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is the presence of insulin. Most NIDDM patients have a normal sequence of the insulin receptor, indicating that, if insulin-receptor mutations contribute to the development of NIDDM, they will be present only in a minor fraction of the NIDDM population. The goal of the present study was to examine whether insulin-receptor mutations contribute to the development of NIDDM. We examined 161 individuals with NIDDM and 538 healthy controls from the population-based Rotterdam study for the presence of mutations in the insulin-receptor gene by SSCP. A heterozygous mutation changing valine-985 into methionine was detected in 5.6% of diabetic subjects and in 1.3% of individuals with normal oral glucose tolerance test. Adjusted for age, gender, and body-mass index, this revealed a relative risk for diabetes of 4.49 (95% confidence interval 1.59-12.25) for Met-985 carriers. When the total study group was analyzed, the prevalence of the mutation increased with increasing serum glucose levels (test for trend P < .005). We conclude that the Met-985 insulin-receptor variant associates with hyperglycemia and represents a risk factor for NIDDM. 30 refs., 3 figs., 1 tab.

  1. Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Munerato Patrícia

    2003-01-01

    Full Text Available Entry of human immunodeficiency type 1 virus (HIV-1 into target cells requires both CD4and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (delta32 within the beta-chemokine receptor 5 gene (CCR5 has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I, with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.

  2. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables

    Science.gov (United States)

    Kasana, Basharat Ahmad; Dar, Waseem Raja; Aziz, Sheikh Aijaz; Lone, Abdul Rashid; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Latief, Muzamil; Arshad, Faheem; Hussain, Moomin; Hussain, Mir

    2016-01-01

    Introduction: Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice. Aims and Objectives: To determine the prevalence of epidermal growth factor receptor (EGFR) mutation in adenocarcinoma lung in a North Indian population and its relation with different clinical variables. Materials and Methods: A total of 57 patients who met inclusion criteria were recruited into the study. Relevant history, clinical examination and investigations were done. EGFR mutation was done in all patients. Results: A total of twenty patients tested positive for EGFR mutation. EGFR was more frequently detected in female patients (53.8%), while as only 19.4% of the male patients expressed EGFR mutation, which was statistically very significant (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as compared to smokers (21.9%) which also was statistically significant (P value of 0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%) as compared to Stage I and II (21.4%) which was statistically significant (P value 0.034). Conclusion: EGFR mutation should be routinely done in all patients of adenocarcinoma lung particularly non-smoker females with Stage III and IV disease. PMID:27688613

  3. -94 G/A polymorphism in the dopamine D1 receptor gene is associated with schizophrenia in a Chinese Han population from Shandong province

    Institute of Scientific and Technical Information of China (English)

    Zhaoyun Du; Guangxin Wang; Yuebing Zhang; Yiren Cheng; Chuanan Zhu

    2011-01-01

    The correlation between-94 G/A polymorphism in the dopamine D1 receptor gene and schizophrenia remains poorly understood despite extensive research.This study sought to evaluate the genotypes and allele frequencies of the-94 G/A polymorphism in the dopamine D1 receptor gene by real-time PCR using TaqMan fluorescent probes.One hundred and sixty-two patients with schizophrenia and 101 healthy controls living in Shandong province of China were evaluated.Experimental results showed that the G/A genotype distribution was significantly higher in the schizophrenia patients than in healthy controls.The frequencies of G allele and A allele were not significantly different between the schizophrenia patients and the controls.Thus,the-94 G/A polymorphism in the dopamine D1 receptor gene was found to be associated with schizophrenia in a Chinese Han population from Shandong province.

  4. Metabotropic glutamate receptor 3 is associated with heroin dependence but not depression or schizophrenia in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Wei Jia

    Full Text Available Metabotropic glutamate receptor subtype 3 (mGluR3, encoded by GRM3 plays important roles in the pathophysiology of schizophrenia, depression, and drug dependence. GRM3 polymorphisms were reported to be associated with prefrontal activity, cognitive shifting, and memory capability in healthy subjects, as well as susceptibility to schizophrenia and depression. The goal of this study was to replicate the association of GRM3 with schizophrenia and depression and to explore GRM3's potential association with heroin dependence (HD in a Chinese population. Seventeen SNPs throughout the GRM3 gene were genotyped using MALDI-TOF within the MassARRAY system, and the allele and genotype distributions were compared between 619 healthy controls and 433 patients with schizophrenia, 409 patients with major depression, and 584 unrelated addicts. We found that GRM3 polymorphisms modulate the susceptibility to HD but do not significantly influence the risk for schizophrenia or depression. An increased risk of HD was significantly associated with the minor alleles of two GRM3 SNPs, including the T allele of rs274618 (Odds ratio (OR = 1.631, 95% confidence interval (95%CI: 1.317-2.005, the T allele of rs274622 (OR = 1.652, 95% CI: 1.336-2.036, compared with the major alleles. The addicts carrying the minor allele of rs274618 or rs274622 had a shortened duration for transition from first use to dependence (DTFUD in comparison to homozygote for major allele (P<0.0001 for each SNP using log rank test. Additionally, a 6-SNP haplotype within 5' region of the GRM3 including the minor alleles of the two aforementioned SNPs was significantly associated with an increased risk of HD (P = 0.00001, OR = 1.668, 95% CI: 1.335-2.084. Our data indicated that GRM3 polymorphisms do not contribute to genetic susceptibility to schizophrenia and depression, but they confer an increased risk of HD in a Chinese population.

  5. Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2015-01-01

    Full Text Available Background: Primary biliary cirrhosis (PBC is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance. The aim of this study was to identify associations between estrogen receptor (ESR gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population. Methods: Thirty-six patients with PBC (case group and 35 healthy individuals (control group from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms (rs2234693, rs2228480, and rs3798577 from ESR1 and two (rs1256030 and rs1048315 from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected. Results: Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872-4.5517. Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577 were risk factors for having PBC. The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR = 5.2469, 95% CI = 1.3704-20.0895 and gamma-glutamyl transferase (OR = 3.4286, 95% CI = 1.0083-13.6578 levels in PBC patients. Conclusions: ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.

  6. Analysis of the association between polymorphisms in the vitamin D receptor (VDR) gene and dental caries in a Chinese population.

    Science.gov (United States)

    Hu, X P; Li, Z Q; Zhou, J Y; Yu, Z H; Zhang, J M; Guo, M L

    2015-09-28

    Environmental influences on the development and progression of dental caries are well known; however, there is little evidence of a genetic component imparting susceptibility to dental caries. The aim of this study was to investigate the relationship between a single nucleotide polymorphism in the vitamin D receptor TaqI locus and dental caries susceptibility in a Chinese population. This case-control study was conducted with a case group (264 patients with dental caries from northwestern China) and a control group (219 individuals without dental caries or systemic disease from the same area). DNA was extracted from the peripheral venous blood of the study participants; the distribution of TaqI locus genotypes and allele frequencies was determined via polymerase chain reaction-restriction fragment length polymorphism. The data obtained were statistically analyzed using the Hardy-Weinberg equilibrium and Chi-square test. The frequency of the Tt genotype in the case group (14.0%) was significantly higher than that in the control group (4.3%), as determined using the genotype TT as the reference. The risk of dental caries was increased 3.8-fold in individuals with the heterozygous Tt genotype compared to that in the individuals with the TT genotype. The proportion of the 't' allele in the case group (7.0%) and the control group (2.1%) was observed to be significantly different [P = 0.0003; OR = 3.592, confidence interval 95% (1.790-7.208)]. Our results therefore suggested that the allele 't' might be a genetic factor determining dental caries susceptibility in individuals from the northwest of China.

  7. Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population: A Case-Control Study

    Institute of Scientific and Technical Information of China (English)

    Liu Yang; Hong Zhang; Yan-Fang Jiang; Qing-Long Jin; Peng Zhang; Xu Li; Pu-Jun Gao

    2015-01-01

    Background: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance.The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population.Methods: Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied.Whole genomic DNA was extracted from all the participants.Three single-nucleotide polymorphisms (rs2234693, rs2228480,and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method.Demographic data and liver biochemical data were collected.Results: Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] =2.1277, 95% confidence interval [CI] =1.1872-4.5517).Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577were risk factors for having PBC.The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR =5.2469,95% CI=1.3704-20.0895) and gamma-glutamyl transferase (OR =3.4286, 95% CI =1.0083-13.6578) levels in PBC patients.Conclusions: ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC.Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.

  8. Levels of Folate Receptor Autoantibodies in Maternal and Cord Blood and Risk of Neural Tube Defects in a Chinese population

    Science.gov (United States)

    Yang, Na; Wang, Linlin; Finnell, Richard H.; Li, Zhiwen; Jin, Lei; Zhang, Le; Cabrera, Robert M.; Ye, Rongwei; Ren, Aiguo

    2016-01-01

    Background After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. Methods From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Results Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71–6.80) and 5.53-fold increased odds (95% CI, 1.90–16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35–2.75) and 3.49 (95% CI, 1.45–8.39), respectively. A dose–response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. Conclusion Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose–response manner. PMID:27166990

  9. Novel Confocal Microscopic and Flow Cytometric Based Assays to Visualize and Detect the (Beta)2-Adrenergic Receptor in Human Lymphocyte and Mononuclear Cell Populations

    Science.gov (United States)

    Salicru, A. N.; Crucian, B. E.; Nelman, M. A.; Sams, C. F.; Actor, J. K.; Marshall, G. D.

    2006-01-01

    The data show that immunophenotyping of leukocyte populations with (beta)2AR is possible with the commercially available Ab, although the FC assay is limited to the IST as a result of the Ab binding site to the intracellular C-terminus of the 2AR. The FC assay has applications for measuring alterations in total (beta)2AR in human leukocyte populations as changes in fluorescence. In addition, CM confirms that both surface and intracellular compartments stain positively for the (beta)2AR and can be used for qualitative assays that screen for changes in receptor compartmentalization and localization.

  10. Variants of the melanocortin 1 receptor gene (MC1R) and P gene would be effective for estimating the population origin of an individual.

    Science.gov (United States)

    Masui, Sosuke; Nakatome, Masato; Matoba, Ryoji

    2009-04-01

    The population origin of an individual is often required to be determined from specimens left at a crime scene for estimating a suspect and individual identity. The melanocortin 1 receptor gene (MC1R) and P gene are associated with human pigmentation. Although there have been several reports that these genes are highly polymorphic in human populations, it is unclear if the allele variants can be used to estimate the population origin of an individual. We aimed to estimate the ethnic origin of a particular individual by using single nucleotide polymorphisms (SNPs). Four SNPs (MC1R gene: R163Q and P gene: IVS5+1001, IVS13+113 and H615R) were genotyped in 394 volunteers from 4 ethnically defined populations using a PCR-based assay. The results revealed that the allele variants were present with high frequency in Asian populations but were low in European and African populations. On the basis of these results, we defined a specific combination of a genotype (R163Q) and a diplotype group (IVS5+1001, IVS13+113 and H615R). This study indicates that the specific combination of a genotype and a diplotype group would be effective for estimating the population origin of an individual from a list of population groups.

  11. Variants of the melanocortin 1 receptor gene (MC1R) and P gene as indicators of the population origin of an individual.

    Science.gov (United States)

    Masui, Sosuke; Nakatome, Masato; Matoba, Ryoji

    2009-05-01

    The population origin of an individual is often requested to be determined from specimens left at a crime scene for identifying a suspect and individual identity. The melanocortin 1 receptor gene (MC1R) and P gene are associated with human pigmentation. Although several studies have reported that these genes are highly polymorphic in human populations, it is unclear if the allele variants can be used to determine the population origin of an individual. We aimed to determine the ethnic origin of an individual by using single nucleotide polymorphisms (SNPs). Eighteen SNPs in the MC1R gene and P genes were genotyped in 52 individuals by the direct sequencing method, and 4 SNPs (MC1R gene: R163Q and P gene: IVS5 + 1001, IVS13 + 113, and H615R) were selected on the basis of differences in frequencies. Subsequently, we genotyped these four SNPs in 422 volunteers from six ethnically defined populations using a polymerase chain reaction-based assay. The results revealed that the allele variants were present with high frequencies in Asian populations but were low in European and African populations. On the basis of these results, we defined a specific combination of a genotype (R163Q) and a diplotype group (IVS5 + 1001, IVS13 + 113, and H615R). This study indicates that the specific combination of a genotype and a diplotype group would be effective in estimating the population origin of an individual from a list of population groups.

  12. Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism

    OpenAIRE

    Kailash Singh; Aung Moe Zaw; Revathi Sekar; Ahuja Palak; Allam, Ahmed A.; Jamaan Ajarem; Chow, Billy K. C.

    2016-01-01

    Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2 adrenergic receptor remains constant during the risk of heart failure. Beta blockers—the antagonistic molecules for beta-adrenergic receptors, function by slowing the heart rate, which there...

  13. Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations

    DEFF Research Database (Denmark)

    Benzinou, Michael; Chèvre, Jean-Claude; Ward, Kirsten J

    2008-01-01

    The therapeutic effects of cannabinoid receptor blockade on obesity-associated phenotypes underline the importance of the endocannabinoid pathway on the energy balance. Using a staged-approach, we examined the contribution of the endocannabinoid receptor 1 gene (CNR1) on obesity and body mass index...

  14. Different patterns of Toll-like receptor 2 polymorphisms in populations of various ethnic and geographic origins.

    NARCIS (Netherlands)

    Ioana, M.; Ferwerda, B.; Plantinga, T.S.; Stappers, M.H.T.; Oosting, M.; McCall, M.B.B.; Cimpoeru, A.; Burada, F.; Panduru, N.; Sauerwein, R.W.; Doumbo, O.; Meer, J.W.M. van der; Crevel, R. van; Joosten, L.A.B.; Netea, M.G.

    2012-01-01

    Upon the invasion of the host by microorganisms, innate immunity is triggered through pathogen recognition by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various m

  15. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

    Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

  16. Biphasic dose-dependent modulation of cardiac parasympathetic activity by moxonidine, an imidazoline I1-receptor agonist.

    Science.gov (United States)

    Turcani, Marian

    2008-12-01

    Peripheral beta-adrenergic blockade and activation of central alpha2-adrenergic receptors have parasympathomimetic effects. The impact of activation of central imidazoline I1-receptors on vagal activity is not yet clear, but there is some evidence that imidazoline I1-receptors agonists may inhibit the parasympathetic system. Parasympatholytic effects may represent a risk for patient with reduced parasympathetic activity. To clarify the effect of imidazoline I1-receptors stimulation on vagal activity, increasing doses of moxonidine were applied subcutaneously to rats with implanted telemetric transmitters. Heart rate and blood pressure variability and baroreflex sensitivity were analyzed. Both, low (0.04, 0.12, and 0.36 mg/kg) and high (1.08 and 3.24 mg/kg), doses of moxonidine reduced the low-frequency power of systolic pressure variability, an index of sympathetic vascular modulation. Despite this reduction, low moxonidine doses neither reduced heart rate nor increased baroreflex gain. A decline of very low frequency power of heart rate variability, a sign of parasympatholysis, was observed with low doses of moxonidine, which can explain the absence of change in heart rate. High doses of moxonidine profoundly augmented very low and high-frequency power of heart rate variability and baroreflex sensitivity. These data suggest that the stimulation of imidazoline I1-receptors is not only sympatholytic but also seems to have as well a weak parasympatholytic effect. However, high doses of moxonidine are strongly parasympathomimetic through the activation of central alpha2-adrenoceptors. Recruitment of alpha2-adrenoceptors also results in manifestation of several side effects.

  17. Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.

    Directory of Open Access Journals (Sweden)

    Stephanie Georgina Dakin

    Full Text Available Macrophages (Mφ orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mφ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured, sub-acute (3-6 weeks post injury and chronically injured (>3 months post injury superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mφ sub-populations were quantified based on surface antigen expression of CD172a (pan Mφ, CD14(highCD206(low (pro-inflammatory M1Mφ, and CD206(high (anti-inflammatory M2Mφ to assess potential polarised phenotypes. In addition, the Lipoxin A(4 receptor (FPR2/ALX was used as marker for resolving inflammation. Normal tendons were negative for both Mφ and FPR2/ALX. In contrast, M1Mφ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mφ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mφ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A(4 (LXA(4 production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E(2. Stimulation with either mediator induced LXA(4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this

  18. HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations.

    Science.gov (United States)

    Jacobs, Michelle M; Murray, Jacinta; Byrd, Desiree A; Hurd, Yasmin L; Morgello, Susan

    2013-10-01

    It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P < 0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

  19. Cardiac Function in Patients with Early Cirrhosis during Maximal Beta-Adrenergic Drive

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Dahl, Emilie Kristine

    2014-01-01

    BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS: Nineteen patients with Child...

  20. Beta adrenergic blockade in the treatment of sustained ventricular tachycardia or ventricular fibrillation

    NARCIS (Netherlands)

    Wiesfeld, ACP; Crijns, HJGM; Tuininga, YS; Lie, KI

    1996-01-01

    The value of beta-blockers as antiarrhythmic drugs in patients with sustained VT or VF has received only little attention. This article summarizes the current state of knowledge regarding the identification of patients with sustained VT or VF with the highest benefit of beta-blockade. The antiarrhyt

  1. The Effect of Beta Adrenergic Blockade on Ratings of Perceived Exertion.

    Science.gov (United States)

    1984-01-01

    more favorable approach to this form of therapy can be taken by those who have ques- tioned the efficacy of using beta blockers and exercise training...also consider the effects of beta blockers on exercise prescrip- .tion. Current guidelines by the American College of Sports V% % Z..w .. - L i V % 3...differences between cardioselective and nonselective beta blockers were evaluated. RPE has been described as a useful indicator nf the relative physiological

  2. Beta-adrenergic stimulation reverses the IKr–IKs dominant pattern during cardiac action potential

    Science.gov (United States)

    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T.; Chen-Izu, Ye

    2014-01-01

    β-adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of IKs, IKr, and IK1 current in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study we used an innovative AP-clamp Sequential Dissection technique to directly record the dynamic –IKs, IKr, IK1– currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of IKs, IKr, IK1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced IKs, moderately increased IK1, but slightly decreased IKr in a dose-dependent manner. The dominance pattern of the K+ currents was IKr>IK1>IKs at the control condition, but reversed to IKr

  3. Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644...... matter, metabolizable energy and digestible protein was of the same magnitude for all groups. The beta-agonist had no significant effect on protein digestibility and metabolizability of energy, but daily live weight gain was significantly higher in the treated bulls. The utilization of digested protein...... was strongly influenced by treatment, with the highest values for Group 2 in both sections. The protein retention increased with 25% in Group 2, with the highest increment of 113 g/d in Section B. The fat retention decreased in treated animals, most pronounced in Group 3, where the reduction was about 50...

  4. Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockade

    DEFF Research Database (Denmark)

    Seifert, T.; Rasmussen, P.; Secher, Niels H.

    2009-01-01

    AIM: Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. METHODS: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion...... with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension...

  5. Oxidation of nutrients in bull calves treated with beta-adrenergic agonists

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    Oxidation of protein (OXP), carbohydrate (OXCHO) and fat (OXF) was investigated with 12 growing bulls treated with beta-agonist (L-644, 969) during two 6 weeks trials (Section A and B) at a mean live weight of 195 and 335 kg. Heat production and nutrient oxidation was calculated from gas exchange......, with CO2 reduced for CO2 from fermentation processes, and nitrogen excretion in urine. The beta-agonist had no effect on the level of rumen fermentation as indicated by the same methane production for control and treated animals. Heat Production (HE, RQx) increased by the treatment of beta......-agonist corresponding to the increment in the protein retention. OXP/HE,RQx was reduced to about 10% in treated animals, indicating that in order to supply amino acids for an increased protein deposition oxidation of protein is decreased. OXF/HE,RQx were markedly higher in treated animals, but as indicated by the same...

  6. Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route.

    Science.gov (United States)

    Antonio, Y; Camargo, C; Galeazzi, E; Iriarte, J; Guzman, M; Muchowski, J M; Gerrity, K; Liu, F; Miller, L M; Strosberg, M M

    1978-01-01

    The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.

  7. Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Swenson, E.R.

    1986-06-01

    Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation.

  8. Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.

    Directory of Open Access Journals (Sweden)

    Pauline Chaste

    Full Text Available Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD. However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls. Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.

  9. Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Anestis, Aristomenis;

    2011-01-01

    Although animal studies indicate that liver X receptor alpha (LXRa) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRa associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the ge......Although animal studies indicate that liver X receptor alpha (LXRa) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRa associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels...

  10. Genetic variation in liver x receptor alpha and risk of ischemic vascular disease in the general population

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Anestis, Aristomenis;

    2011-01-01

    Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the ge......Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels...

  11. Toll-like receptor 4 polymorphism impairing lipopolysaccharide signaling in Sus scrofa, and its restricted distribution among Japanese wild boar populations.

    Science.gov (United States)

    Shinkai, Hiroki; Okumura, Naohiko; Suzuki, Rintaro; Muneta, Yoshihiro; Uenishi, Hirohide

    2012-04-01

    Toll-like receptor 4 (TLR4) responds to lipid A, the active moiety of lipopolysaccharide from gram-negative bacteria, in cooperation with myeloid differentiation protein-2 and plays a vital role in innate immunity. Polymorphisms in TLR4 are associated with changes in susceptibility to various infectious diseases. We previously found seven amino acid polymorphisms in Sus scrofa TLR4. In this study, we showed by luciferase reporter assay that an alteration from cysteine to tryptophan at position 506 (C506W) caused loss of ability to induce nuclear factor-κB activation after lipid A stimulation. This polymorphism was found only in Japanese wild boar (JWB) populations of S. scrofa. Genotyping of TLR4 in different JWB populations revealed that C506W polymorphism was under pressure from purifying selection in a local population (Tajima's D=-0.98; p<0.05). However, in another population, this polymorphism existed at a frequency such that homozygous animals with the W506 alleles seldom appeared. These findings suggest that the C506W polymorphism is under different types of pressure by natural selection between populations, which may reflect differences in residential pathogens or demographic factors.

  12. Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population

    DEFF Research Database (Denmark)

    Nissen, Peter H; Christensen, Signe E; Heickendorff, Lene

    2007-01-01

    hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. OBJECTIVE: We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. DESIGN AND PARTICIPANTS...... calcium concentrations moderately above the upper reference limit, to calcium levels more than 20% above the upper reference limit. Furthermore, the mean plasma PTH concentration was within the normal range in eight of 11 studied mutations, but mild to moderately elevated in families with the mutations p...

  13. Common Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations

    DEFF Research Database (Denmark)

    Dube, J. B.; Wang, J.; Cao, H.;

    2015-01-01

    BACKGROUND: Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p......10(-49)), which was >3x larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7x10(-17)), but did not have classical familial hypercholesterolemia...

  14. Lack of association between neuropeptide S receptor 1 gene (NPSR1) and eczema in five European populations.

    NARCIS (Netherlands)

    Ekelund, E.; Bradley, M.; Weidinger, S.; Jovanovic, D.L.; Johansson, C.; Lindgren, C.M.; Todorova, A.; Jakob, T.; Illig, T.; von Mutius, E.; Braun-Fahrlander, C.; Doekes, G.; Riedler, T.; Scheynius, A.; Pershagen, G.; Kockum, I.; Kere, J.

    2009-01-01

    Eczema is often associated with development of allergic asthma. The Neuropeptide S Receptor 1 (NPSR1) gene has previously been associated with asthma and elevated serum IgE levels. The aim of this study was to investigate a potential association between the NPSR1 gene and eczema in patients and heal

  15. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

    Science.gov (United States)

    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...

  16. Population and pedigree studies reveal a lack of association between the dopamine D sub 2 receptor gene and alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Bolos, A.M.; Goldman, D.; Brown, G.L. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (USA)); Lucas-Derse, S.; Ramsburg, M. (Program Resources Inc., Frederick, MD (USA))

    1990-12-26

    Using the dopamine D{sub 2} receptor clone {lambda}hD2G1, Blum et al recently found that the D{sub 2}/Taq 1 allele (A1) was present in 69{percent} of 35 deceased alcoholics but in only 20{percent} of an equal number of controls. To assess this association further, the authors evaluated the D{sub 2}/Taq 1 polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3{prime} noncoding region of the D{sub 2} receptor gene. They studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D{sub 2}/Taq 1 or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D{sub 2} receptor locus. This study does not support a widespread or consistent association between the D{sub 2} receptor gene and alcoholism.

  17. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

    DEFF Research Database (Denmark)

    Hansen, P.S.; Deure, W.M. van der; Peeters, R.P.;

    2007-01-01

    OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...

  18. Relation between serum xenobiotic induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations

    DEFF Research Database (Denmark)

    Long, Manhai; Stronati, Alessanda; Bizzaro, Davide;

    2007-01-01

    -mediated luciferase reporter gene expression. Sperm DNA damage was measured using terminal deoxynucleotidyl transferase-driven dUTP nick labeling assay (TUNEL) and pro- (Fas) and anti-apoptotic (Bcl-xL) markers were determined by immune methods. Different features of xenobiotic-induced receptor activity in serum...

  19. Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine.

    Science.gov (United States)

    Mobini, Reza; Fu, Michael; Jansson, Per-Anders; Bergh, Claes-Håkan; Scharin Täng, Margareta; Waagstein, Finn; Andersson, Bert

    2006-03-01

    Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

  20. Quantitation of alpha 1-adrenergic receptors in porcine uterine and mesenteric arteries

    Energy Technology Data Exchange (ETDEWEB)

    Farley, D.B.; Ford, S.P.; Reynolds, L.P.; Bhatnagar, R.K.; Van Orden, D.E.

    1984-11-01

    The activation of vascular alpha-adrenergic receptors may be involved in the control of uterine blood flow. A radioligand binding assay with the use of the alpha 1-adrenergic antagonist /sup 3/H-WB-4101 was established to characterize the alpha-adrenergic receptors in uterine and mesenteric arterial membranes obtained from nonpregnant pigs. Specific binding of /sup 3/H-WB-4101 was rapid, saturable, and exhibited the alpha-adrenergic agonist potency order of (-)-epinephrine inhibition constant (Ki) . 0.6 mumol/L greater than (-)-norepinephrine (Ki . 1.5 mumol/L) much greater than (-)-isoproterenol (Ki . 120 mumol/L). The alpha-adrenergic antagonist phentolamine (Ki . 6.0 nmol/L) was 200 times more potent than the beta-adrenergic antagonist (+/-)-propranolol (Ki . 1,200 nmol/L); the alpha 1-selective antagonist prazosin (Ki . 1.2 nmol/L) was 130 times more potent than the alpha 2-selective antagonist yohimbine (Ki . 160 nmol/L). Scatchard analysis, as well as iterative curve-fitting analysis, demonstrated that /sup 3/H-WB-4101 binding by arterial membranes was to a single class of binding sites. Uterine arteries exhibited greater maximal binding capacity (BMax) than that of mesenteric arteries (47.5 +/- 3.2 versus 30.9 +/- 3.6 fmol per milligram of protein, p less than 0.01), but the uterine artery dissociation constant (Kd) was higher, thus indicating a lower affinity, when compared with mesenteric artery (0.43 +/- 0.04 versus 0.33 +/- 0.04 nmol/L, p less than 0.05).

  1. Systematic screening for mutations in the human N-methyl-D-aspartate receptor 1 gene in schizophrenic patients from the German population.

    Science.gov (United States)

    Paus, Sebastian; Rietschel, Marcella; Schulze, Thomas G; Ohlraun, Stephanie; Diaconu, Carmen C; Van Den Bogaert, Ann; Maier, Wolfgang; Propping, Peter; Cichon, Sven; Nöthen, Markus M

    2004-12-01

    Evidence for a dysfunction of the N-methyl-D-aspartate (NMDA) type of ionotropic glutamate receptors in schizophrenic patients, comes from neurochemical and clinical pharmacologic data. Therefore, the NMDAR1 gene can be regarded as an interesting candidate gene for schizophrenia. Several groups have tried to identify variants of this gene in schizophrenic patients in different, however not in German, populations. We sought to identify sequence changes of potential functional relevance in genomic DNA from 46 German unrelated schizophrenic patients by means of single-strand conformation analysis. No mutations of likely functional relevance were observed. We identified two synonymous coding Single Nucleotide Polymorphisms (cSNPs) in exons 6 and 7, and two SNPs in exon-flanking intronic sequences. Genotype distribution of these four SNPs was not significantly different between schizophrenic patients and controls. Our results suggest that the NMDAR1 subunit is not frequently involved in the development of schizophrenia in the German population.

  2. Genetic drift outweighs natural selection at toll-like receptor (TLR) immunity loci in a re-introduced population of a threatened species.

    Science.gov (United States)

    Grueber, Catherine E; Wallis, Graham P; Jamieson, Ian G

    2013-09-01

    During population establishment, genetic drift can be the key driver of changes in genetic diversity, particularly while the population is small. However, natural selection can also play a role in shaping diversity at functionally important loci. We used a well-studied, re-introduced population of the threatened Stewart Island robin (N = 722 pedigreed individuals) to determine whether selection shaped genetic diversity at innate immunity toll-like receptor (TLR) genes, over a 9-year period of population growth following establishment with 12 genetic founders. We found no evidence for selection operating with respect to TLR diversity on first-year overwinter survival for the majority of loci, genotypes and alleles studied. However, survival of individuals with TLR4BE genotype was significantly improved: these birds were less than half as likely to die prior to maturity compared with all other TLR4 genotypes. Furthermore, the population frequency of this genotype, at a two-fold excess over Hardy-Weinberg expectation, was increased by nonrandom mating. Near-complete sampling and full pedigree and reproductive data enabled us to eliminate other potential causes of these patterns including inbreeding, year effects, density dependence, selection on animals at earlier life history stages or genome-level association of the TLR4E allele with 'good genes'. However, comparison of observed levels of gene diversity to predictions under simulated genetic drift revealed results consistent with neutral expectations for all loci, including TLR4. Although selection favoured TLR4BE heterozygotes in this population, these effects were insufficient to outweigh genetic drift. This is the first empirical study to show that genetic drift can overwhelm natural selection in a wild population immediately following establishment.

  3. Association of Fc gamma-receptors IIa, IIIa, and IIIb genetic polymorphism with susceptibility to chronic periodontitis in South Indian population

    Directory of Open Access Journals (Sweden)

    Veenu Madaan Hans

    2015-01-01

    Full Text Available Background and Objective: Fc gamma receptors (FcγRs are the members of the immunoglobulin superfamily and may play a role in the pathogenesis of periodontitis. Genetic variation in these receptors and its link with various forms of periodontitis is being studied in different populations. The aim of the present study is to determine whether specific FcγRIIa, FcγRIIIa, and FcγRIIIb alleles and/or genotypes are associated with risk for susceptibility to generalized chronic periodontitis (GCP in South Indian population. Materials and Methods: The study population consisted of 120 South Indian subjects; 60 with GCP and 60 periodontally healthy. Deoxyribonucleic acid (DNA was extracted from samples collected by scrapping buccal epithelium. FcγRIIa and FcγRIIIa genotyping were performed by polymerase chain reaction (PCR amplification of DNA with allele-specific primers followed by allele-specific restriction digestion of the products. However, FcγRIIIb genotyping was done by allele-specific PCR. Results: No significant difference in the distribution of FcγRIIa H/R and FcγRIIIa NA1/NA2 genotypes or their respective alleles was observed in GCP patients and healthy subjects. For FcγRIIIa F/V genetic polymorphism, the homozygous V/V genotype and V allele were significantly overrepresented in GCP patients while F/F genotype and F allele in controls. Conclusion: The present study demonstrates that FcγRIIIa V/V genotype, as well as V allele, could be a possible risk factor for chronic periodontitis in South Indian population.

  4. Dobutamine stress echo is superior to exercise stress testing in achieving target heart rate among patients on beta blockers.

    Science.gov (United States)

    Sabbath, Adam; Pack, Michael; Markiewicz, Richard; John, Jooby; Gaballa, Mohamed; Goldman, Steven; Thai, Hoang

    2005-01-01

    Published guidelines recommend continuing beta-adrenergic receptor blockade in patients undergoing stress testing. We evaluated the role of pharmacological versus exercise stress testing in achieving target heart rate (THR) among patients on beta-adrenergic blockade. We compared data from 140 patients who underwent dobutamine stress echo (DSE) and 143 patients who underwent exercise treadmill testing (ETT). In both groups, beta-adrenergic blocker was continued at the time of stress testing. Overall, patients undergoing DSE achieved THR more frequently than ETT. With beta-adrenergic blockade, DSE patients met THR more frequently than ETT patients (p < 0.001). Without beta-adrenergic blockade, there was no difference between either modality in achieving THR. In both DSE and ETT patients, absence of beta-adrenergic blockade increased the odds of achieving THR [odds ratio (OR): 2.46, p = 0.042 and OR: 7.44, p < 0.001, respectively]. Atropine use with DSE increased the odds of achieving THR (OR: 3.76, p = 0.006). In conclusion, pharmacological stress testing appears to be superior to exercise stress testing in achieving THR among patients on beta-adrenergic blockade.

  5. The T945M Single Nucleotide Polymorphism of the Bovine Leptin Receptor Gene in Population of Slovak Spotted Bulls

    Directory of Open Access Journals (Sweden)

    Anna Trakovická

    2011-09-01

    Full Text Available The objective of this study was detection of DNA polymorphism of the leptin receptor gene using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. The SNP T945M, which maps on bovine chromosome 3 at the exon 20 of the leptin receptor sequence and corresponds to a mutation in the intracellular region of the functional protein, was also analyzed. In exon 20, a T to C missense mutation was found at nucleotide 115, which causes an amino acid substitution at residue 945 (T954M. The polymorphism of leptin receptor gene was studied in a group of 57 bulls of Slovak spotted breed. A strategy employing PCR was used to amplify 197 bp products from blood samples. Digestion of PCR products with restriction enzyme BseGI revealed two alleles: allele C was 130 and 67 fragments and allele T was 93, 67 and 37. Frequencies for allele C and T were 0.9737 and 0.0263, respectively and TT genotype was not detected.

  6. Assessment of the link between Vitamin D receptor TaqI gene polymorphism and periodontitis: a meta-analysis in a Chinese population.

    Science.gov (United States)

    Ji, X W; Wang, Y; Cao, C; Zhong, L J

    2016-10-06

    Although a number of studies have been conducted to determine the association between vitamin D receptor (VDR) TaqI polymorphism and periodontitis in the Chinese population, this association remains elusive. To assess the influence of VDR TaqI polymorphism on the risk of periodontitis, a meta-analysis was performed in a Chinese population. Relevant studies were identified using the databases PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, through January 2016. Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations. This meta-analysis identified 9 studies, which included 1014 periodontitis cases and 907 controls. In both overall and subgroup analyses, VDR TaqI polymorphism was not associated with the risk of periodontitis. Cumulative analysis also suggested a lack of association between VDR TaqI polymorphism and the risk of periodontitis in the Chinese population. In conclusion, our meta-analysis showed that VDR TaqI polymorphism is not associated with the risk of periodontitis in the Chinese population. Further studies in other ethnic groups are required for definite conclusions.

  7. Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

    Science.gov (United States)

    Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

    2008-11-01

    Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

  8. Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample.

    Directory of Open Access Journals (Sweden)

    A Mobascher

    Full Text Available Variation in genes coding for nicotinic acetylcholine receptor (nAChR subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP, an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.

  9. Genetic association between the dopamine D1-receptor gene and paranoid schizophrenia in a northern Han Chinese population

    Directory of Open Access Journals (Sweden)

    Yao J

    2014-04-01

    Full Text Available Jun Yao, Mei Ding, Jiaxin Xing, Jinfeng Xuan, Hao Pang, Yuqing Pan, Baojie WangInstitute of Forensic Medicine, China Medical University, Shenyang, People's Republic of ChinaObjective: Dysregulation of dopaminergic neurotransmission at the D1 receptor in the prefrontal cortex has been implicated in the pathogenesis of schizophrenia. Genetic polymorphisms of the dopamine D1-receptor gene have a plausible role in modulating the risk of schizophrenia. To determine the role of DRD1 genetic polymorphisms as a risk factor for schizophrenia, we undertook a case-control study to look for an association between the DRD1 gene and schizophrenia.Materials and methods: We genotyped eleven single-nucleotide polymorphisms within the DRD1 gene by deoxyribonucleic acid sequencing involving 173 paranoid schizophrenia patients and 213 unrelated healthy individuals. Statistical analysis was performed to identify the difference of genotype, allele, or haplotype distribution between cases and controls.Results: A significantly lower risk of paranoid schizophrenia was associated with the AG + GG genotype of rs5326 and the AG + GG genotype of rs4532 compared to the AA genotype and the AA genotype, respectively. Distribution of haplotypes was no different between controls and paranoid schizophrenia patients. In the males, the genotype distribution of rs5326 was statistically different between cases and controls. In the females, the genotype distribution of rs4532 was statistically different between cases and controls. However, the aforementioned statistical significances were lost after Bonferroni correction.Conclusion: It is unlikely that DRD1 accounts for a substantial proportion of the genetic risk for schizophrenia. As an important dopaminergic gene, DRD1 may contribute to schizophrenia by interacting with other genes, and further relevant studies are warranted.Keywords: dopamine D1 receptor, paranoid schizophrenic, single-nucleotide study, association, genetic

  10. DEGRANULATION OF RAT SALIVARY-GLANDS FOLLOWING TREATMENT WITH RECEPTOR-SELECTIVE AGONISTS

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; SGRAVENMADE, EJ; KONINGS, AWT

    1995-01-01

    1. The aim of this study was to find a drug that induces an almost complete degranulation of secretory cells in rat parotid and submandibular glands. 2. Phenylephrine (alpha-adrenergic), isoproterenol (beta-adrenergic) and mecholine (muscarinic cholinergic) were tested. Time and degree of maximal de

  11. Characterization of surface interleukin-2 receptor expression on gated populations of peripheral blood mononuclear cells from manatees, Trichechus manatus latirostris.

    Science.gov (United States)

    Sweat, J M; Johnson, C M; Marikar, Y; Gibbs, E P

    2005-12-15

    An in vitro system to determine surface interleukin-2 receptor (IL-2R) expression on mitogen-stimulated peripheral blood mononuclear cells (PBMC) from free-ranging manatees, Trichechus manatus latirostris was developed. Human recombinant IL-2, conjugated with a fluorescein dye was used in conjunction with flow cytometric analysis to determine changes in surface expression of IL-2R at sequential times over a 48-h period of in vitro stimulation. Surface expression of IL-2R was detected on manatee PBMC, which also cross-reacted with an anti-feline pan T-cell marker. An expression index (EI) was calculated by comparing mitogen-activated and non-activated PBMC. Based on side- and forward-scatter properties, flow cytometric analysis showed an increase in the number of larger, more granular "lymphoblasts" following concanavalin A (Con A) stimulation. The appearance of lymphoblasts was correlated with an increase in their surface expression of IL-2 receptors. Surface IL-2R expression, in Con A-stimulated PBMC, was detected at 16 h, peaked at 24-36 h, and began to decrease by 48 h. Characterization of the IL-2R expression should provide additional information on the health status of manatees, and the effect of their sub lethal exposure to brevetoxin.

  12. POLYMORPHISM OF PROLACTIN RECEPTOR GENE (PRLR IN THE POLISH LANDRACE AND POLISH LARGE WHITE SWINE POPULATION AND REPRODUCTIVE TRAITS

    Directory of Open Access Journals (Sweden)

    AGATA ZIÓŁKOWSKA

    2011-01-01

    Full Text Available Prolactin receptor gene was found in pig chromosome 16, and it is one of the genes with a significant effect on reproduction traits in sows. The objective of the research was to determine polymorphism of the prolactin receptor gene in pigs of two maternal breeds: Polish Landrace and Polish Large White, as well as analyse relations between particular allelomorphic variants, and reproduction traits of examined sows. Two PRLR gene alleles, A and B, were isolated, they were obtained after AluI restriction gene digestion of the PCR product with the length of 163 bp; furthermore, three genotypes were identified: PRLRAA – 85, 59, 19 bp; PRLRAB – 104, 85, 59, 19 bp; PRLRBB – 104, 59 bp. We assessed 122 sows, in terms of their age at the first farrowing, as well as the sizes of the two subsequent litters. No statistically significant differences were found in the examined reproduction traits in sows with different allelomorphic relations, both within each breed and between breeds. Obtained results indicate that it is necessary to conduct further research on a larger animal group.

  13. Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

    Institute of Scientific and Technical Information of China (English)

    Georgios Megas; Michael Chrisofos; Ioannis Anastasiou; Aida Tsitlidou; Theodosia Choreftaki; Charalampos Deliveliotis

    2015-01-01

    The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow‑up were 64.2 and 6 years, respectively. The HSCORE was used for semi‑quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

  14. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

    DEFF Research Database (Denmark)

    Hansen, Pia Skov; van der Deure, Wendy M; Peeters, Robin P;

    2007-01-01

    OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size......, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations...... between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84...

  15. TetraMabs: simultaneous targeting of four oncogenic receptor tyrosine kinases for tumor growth inhibition in heterogeneous tumor cell populations

    Science.gov (United States)

    Castoldi, Raffaella; Schanzer, Jürgen; Panke, Christian; Jucknischke, Ute; Neubert, Natalie J.; Croasdale, Rebecca; Scheuer, Werner; Auer, Johannes; Klein, Christian; Niederfellner, Gerhard; Kobold, Sebastian; Sustmann, Claudio

    2016-01-01

    Monoclonal antibody-based targeted tumor therapy has greatly improved treatment options for patients. Antibodies against oncogenic receptor tyrosine kinases (RTKs), especially the ErbB receptor family, are prominent examples. However, long-term efficacy of such antibodies is limited by resistance mechanisms. Tumor evasion by a priori or acquired activation of other kinases is often causative for this phenomenon. These findings led to an increasing number of combination approaches either within a protein family, e.g. the ErbB family or by targeting RTKs of different phylogenetic origin like HER1 and cMet or HER1 and IGF1R. Progress in antibody engineering technology enabled generation of clinical grade bispecific antibodies (BsAbs) to design drugs inherently addressing such resistance mechanisms. Limited data are available on multi-specific antibodies targeting three or more RTKs. In the present study, we have evaluated the cloning, eukaryotic expression and purification of tetraspecific, tetravalent Fc-containing antibodies targeting HER3, cMet, HER1 and IGF1R. The antibodies are based on the combination of single-chain Fab and Fv fragments in an IgG1 antibody format enhanced by the knob-into-hole technology. They are non-agonistic and inhibit tumor cell growth comparable to the combination of four parental antibodies. Importantly, TetraMabs show improved apoptosis induction and tumor growth inhibition over individual monospecific or BsAbs in cellular assays. In addition, a mimicry assay to reflect heterogeneous expression of antigens in a tumor mass was established. With this novel in vitro assay, we can demonstrate the superiority of a tetraspecific antibody to bispecific tumor antigen-binding antibodies in early pre-clinical development. PMID:27578890

  16. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles.

    Science.gov (United States)

    Puck, Jennifer M

    2012-03-01

    The most profound primary immunodeficiency disease, severe combined immunodeficiency (SCID), is fatal in infancy unless affected infants are provided with an adaptive immune system through allogeneic hematopoietic cell transplantation, enzyme replacement, or gene therapy. However, most infants with SCID lack a family history or any clinical clues before the onset of infections, making this serious but treatable disease a candidate for population-based newborn screening. Of several approaches considered for SCID screening, testing for T-cell receptor excision circles (TRECs), a DNA biomarker of normal T-cell development, has proved successful. TREC numbers can be measured in DNA isolated from the dried bloodspots already routinely collected for newborn screening. Infants with low or absent TRECs can thus be identified and referred for confirmatory testing and prompt intervention. TREC testing of newborns is now being performed in several states, indicating that this addition to the newborn screening panel can be successfully integrated into state public health programs.

  17. Effects and mechanism of different adrenergic receptor antagonists on left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats

    Institute of Scientific and Technical Information of China (English)

    HU Qin; LI Long-gui; ZHANG Yun

    2004-01-01

    To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the ef-fects of three kinds of adrenergic receptor blockers: Carvedilol (CAR), Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypearophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA) was used in this study. Thirty two male istar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER.emodynamics, ventric-ular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ /Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ/Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ/Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was indepen-dent of beta-adrenergic receptor antagonist.

  18. Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population

    Science.gov (United States)

    Mahjoubi, Imen; Kallel, Amani; Sbaï, Mohamed Hédi; Ftouhi, Bochra; ben Halima, Meriam; Jemaa, Zeineb; Feki, Moncef; Slimane, Hedia; Jemaa, Riadh; Kaabachi, Naziha

    2016-01-01

    Background & objectives: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population. Methods: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577). Interpretation & conclusions: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population. PMID:27834325

  19. Significant Association Between Fc Receptor-Like 3 Polymorphisms (-1901A>G and -658C>T) and Neuromyelitis Optica (NMO) Susceptibility in the Chinese Population.

    Science.gov (United States)

    Wang, Xinling; Yu, Tao; Yan, Qichang; Wang, Wei; Meng, Nan; Li, Xuejiao; Luo, Yahong

    2016-01-01

    Neuromyelitis optica (NMO) is an autoimmune disorder. In pathogenesis, NMO-immunoglobulin G (NMO-IgG) selectively binds to aquaporin-4 (AQP4) and resulted in neuritis, myelitis, and brain lesion. Fc receptor-like 3 (FCRL3) gene encodes a member of the immunoglobulin receptor superfamily, which plays an important part in regulating immune activities. This study aimed at investigating the association between FCRL3 polymorphisms and NMO susceptibility and, hopefully, to contribute to the development of novel methods for diagnosis and treatment of NMO. We selected 150 NMO patients and 300 healthy controls from the Chinese population. Tag single nucleotide polymorphisms (SNPs) were identified with reference to CBI-dbSNP and HapMap databases. DNA were extracted and amplified. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determine the polymorphisms. χ (2), odds ratio (OR), and 95 % confidence interval (95 % CI) were presented to evaluate genotype distribution and association between SNPs and NMO susceptibility. Six out of 15 SNPs were selected according to the filter. No significant altered genotype distribution was observed concerning -11G>C, -166C>T, -219G>C, and -1629C>G polymorphisms. The G allele of -1901A>G variation was demonstrated to be more frequent in patients compared with controls (P T polymorphism was significantly more prevalent in NMO patients than controls (P = 0.009). In summary, the study revealed that the G allele in -1901A>G polymorphism and T allele in -658C>T polymorphism are genetic risk factors for NMO in the Chinese population. Further research is needed to account for different ethnicities and clarify the mechanisms behind, which might contribute to the elucidation of novel diagnosis methods.

  20. Cardiac beta-receptors in experimental Chagas' disease Receptores beta cardíacos na doença de Chagas experimental

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    Julio E. Enders

    1995-02-01

    Full Text Available Experimental Chagas' disease (45 to 90 days post-infection showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase. Chagasic infection did not change the beta receptors density (78.591 ± 3.125 fmol/mg protein and 73.647 ± 2.194 fmol/mg protein for controls but their affinity was significantly diminished (Kd = 7.299 ± 0.426 nM and Kd = 3.759 ± 0.212 nM for the control p Estudaram-se os receptores beta cardíacos de camundongos infectados pelo Trypanosoma cruzi na fase pós-aguda da doença de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anômalas às catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcação dos receptores beta cardíacos dos camundongos normais e dos infectados na fase pós-aguda (45 a 90 dias pós-infecção. O número dos sítios de fixação foi similar nos dois grupos, 78.591 ± 3.125 fmol/mg. Proteína nos chagásicos e 73.647 ± 2.194 fmol/mg. Proteína no grupo controle. Em vez disso, a afinidade verificou-se significativamente diminuida no grupo chagásico (Kd = 7.299 ± 0.426 nM respeito do controle (Kd = 3.759 ± 0.212 nM p < 0.001. Os resultados obtidos demonstram que as modificações observadas na estimulação adrenérgica do miocárdio chagásico se correlacionam com a menor afinidade dos receptores beta cardíacos e que estas alterações exerceriam uma parte determinante para as consequências funcionais que são detectadas na fase crônica.

  1. Vitamin D receptor gene polymorphisms in relation to the risk of colorectal cancer in the Polish population.

    Science.gov (United States)

    Laczmanska, Izabela; Laczmanski, Lukasz; Bebenek, Marek; Karpinski, Pawel; Czemarmazowicz, Halina; Ramsey, David; Milewicz, Andrzej; Sasiadek, Maria M

    2014-12-01

    The protective effect of vitamin D against several cancers including colorectal cancer is modulated by the vitamin D receptor (VDR) and its ligand, the active form of vitamin D. VDR response has been found to play a role in various genes encoding proteins involved in crucial cellular pathways. Single nucleotide polymorphisms (SNPs) of the VDR gene that modulate its activity are located in the promoter region, exons 2-9, and their vicinity and also in the 3'UTR region. Some of them have been previously studied in relation to cancer susceptibility and prognosis. The aim of our study was to investigate four polymorphisms, BsmI, ApaI, TaqI, and FokI, of the VDR gene in Polish patients with sporadic colorectal cancer and to evaluate their association with susceptibility to cancer. We found a significant association between the BsmI genotype and cancer (individuals with the bb genotype are more susceptible to cancer compared to those with other genotypes, p = 0.025, Fisher's exact test for 2 × 2 table). Also, the TT genotype at TaqI and the AA genotype at ApaI are correlated with a higher risk of cancer (p = 0.00071 and p = 1.0 × 10(-5), respectively). We found relatively strong linkage disequilibrium between the TaqI and ApaI loci (T with A and t with a, respectively). Both of these loci are associated with cancer. We do not observe any such association for the FokI polymorphism. In conclusion, a small modification in VDR expression may play a role in such a multipathway process as tumorigenesis.

  2. Association between Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population

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    Yong Joo Hong

    2015-12-01

    Full Text Available BackgroundType 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR gene were associated with diabetic complications.MethodsIn present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb polymorphisms.ResultsMean age was 62.44±10.64 years and mean disease duration was 13.65±7.39 years. Patients with B allele (BB or Bb was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68 compared with patients without B allele (bb; 17.3%, 81/469; P=0.035. This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035 in logistic regression analysis.ConclusionOur findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

  3. Synthesis and pharmacological activity of adaprolol enantiomers: a new soft drug for treating glaucoma.

    Science.gov (United States)

    Boder, N; Elkoussi, A; Zuobi, K; Kovacs, P

    1996-01-01

    Adaprolol maleate is a new beta-adrenergic antagonist that is being developed to treat glaucoma. The soft drug was designed to minimize systemic activity through facile inactivation to an inactive metabolite. Studies with other potent beta-adrenergic antagonists indicated that tissue specific receptor differences might be more stringent for selected beta-adrenergic blocking activities and suggested that R enantiomers of traditional beta-blockers should be developed for controlling glaucoma. The present studies demonstrate that the potent ocular hypotensive effects of adaprolol are not stereoselective. In contrast, cardiac effects could be detected after intravenous S(+) adaprolol, but not R(-) adaprolol. The studies confirm that adaprolol functions as a potent beta-adrenergic antagonist. The negligible systemic beta-blocking activity detected with opthalmic administration of adaprolol is consistent with soft drug design.

  4. Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

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    Jing-Cong Zhuang

    2015-01-01

    Full Text Available Background: Neuromyelitis optica (NMO and multiple sclerosis (MS are autoimmune demyelinating diseases of the central nerve system. Interleukin-7 (IL-7 and interleukin-7 receptor alpha (IL-7Rα were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants (rs1520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502 and one variant of IL-7RA (rs6897932 with NMO and MS among Chinese Han population in southeastern China. Methods: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MassARRAY system and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate <90%. Results: Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls (P = 0.035 and 0.034, respectively. There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients (P = 0.014. And there were statistically significant differences in the rs6897932 genotypes (P = 0.004 and alleles (P = 0.042 between NMO-IgG positive patients and healthy controls. Conclusions: The study suggested that among Chinese Han population in southeastern China, the variant of IL-7RA (rs6897932 was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 (rs1520333 with MS patients. And the genotypic differences of IL-7 rs2887502

  5. Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

    Institute of Scientific and Technical Information of China (English)

    Jing-Cong Zhuang; Lei Wu; Mei-Zhen Qian; Ping-Ping Cai; Qi-Bing Liu; Gui-Xian Zhao; Zhen-Xin Li

    2015-01-01

    Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune demyelinating diseases of the central nerve system.Interleukin-7 (IL-7) and interleukin-7 receptor alpha (IL-7Rα) were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes.The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations.However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population.Here, we aimed to evaluate the association of six IL-7 variants (rs 1520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502) and one variant of IL-7RA (rs6897932) with NMO and MS among Chinese Han population in southeastem China.Methods: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MassARRAY system) and Sanger sequencing were used to determine the variants ofIL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China.Samples were excluded if the genotyping success rate <90%.Results: Statistical differences were observed in the genotypes ofIL-7 rs 1520333 in MS patients and IL-7RA rs6897932 in NMO patients,compared with healthy controls (P =0.035 and 0.034, respectively).There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients (P =0.014).And there were statistically significant differences in the rs6897932 genotypes (P =0.004) and alleles (P =0.042) between NMO-IgG positive patients and healthy controls.Conclusions: The study suggested that among Chinese Han population in southeastern China, the variant of IL-7RA (rs6897932) was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 (rs1520333) with MS patients.And the genotypic differences ofIL-7 rs2887502 between MS and NMO

  6. Clinicopathologic Characteristics of Oestrogen Receptor-Positive/Progesterone Receptor-Negative/Her2-Negative Breast Cancer According to a Novel Definition of Negative Progesterone Receptor Status: A Large Population-Based Study from China.

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    An-qi Li

    Full Text Available A lack of progesterone receptor (PgR expression in oestrogen receptor-positive (ER+ tumours is associated with worse survival. PgR status is usually defined as positive or negative using 1% positive nuclei as a cut-off point. In this study, we aimed to assess the clinicopathologic characteristics of ER+/PgR-/HER2- tumours by comparing them with ER+/PgR+/HER2- tumours using a PgR cut-off point of 20% as a divisive criterion.We analysed 1,522 patients with primary breast cancer who had undergone surgery at the Cancer Center of Fudan University between 2012 and 2014. Age, grade, tumour size, lymph node status and lymphovascular invasion were assessed. Multinomial logistic regression, linear regression and chi-square test models were applied to assess associations between ER, PR and clinical features.ER+/PgR-/HER2- tumours showed poorer clinicopathologic characteristics relative to ER+/PgR+/HER2- tumours using a PgR threshold of 20% instead of 1%. The clinicopathologic characteristics did not differ between tumours with purely negative PgR expression and tumours with a PgR percentage ranging from 1% to 19%. The prognostic significance of PR expression appeared more pronounced in patients under a high Ki-67 status than those under a low Ki-67 status.Based on these findings, we propose the use of a novel threshold of 20% to define PgR status. Nevertheless, the impact of this new criterion on patient management and clinical treatment requires additional study.

  7. Clinical expression in heterozygotes of two frequent low density lipoprotein receptor gene mutations in the French Canadian population

    Energy Technology Data Exchange (ETDEWEB)

    Roy, M.; Minnich, A.; Davignon, J. [Clinical Research Institute of Montreal, Quebec (Canada)

    1994-09-01

    Five mutations in the low density lipoprotein (LDL) receptor (R) gene account for approximately 83% of cases of heterozygous familial hypercholesterolemia (hFH) in French Canadians in Quebec. The two most prevalent mutations are a >10kb deletion (10kb) of the promoter region resulting in a null allele (60.5% of cases) and a trp{sub 66}{r_arrow}gly missense mutation in exon 3 (ex3) resulting in a binding-defective R (11.7%). We have compared the phenotypic expression of these two mutations in 427 10kb hFH patients, 239 women (age 37.5 {plus_minus} 14.2 years) and 188 men (33.7 {plus_minus} 11.7) and 69 ex3 hFH patients, 42 women (40.6 {plus_minus} 14.3) and 27 men (36.8 {plus_minus}13.2). All data were analyzed separately for women and men. Tendon xanthomas were more prevalent in the 10kb (women 63%, men 68%) than in the ex3 patients (48%,48%). Total and LDL cholesterol were significantly higher in the 10kb patients with than without xanthomas but similar in ex3 patients. There were no significant differences in plasma lipoprotein concentrations between 10kb and ex3 patients with coronary artery disease (CAD) or between 10kb and ex3 patients without CAD. Among men with CAD, those with 10kb were significantly younger than those with ex3 (39.6 {plus_minus} 9.8, n=93 and 46.4 {plus_minus} 7.0, n=9, respectively). In both sexes, high plasma lipoprotein concentrations conferred an increased risk of CAD in 10kb but not in ex3 patients. Thus, as in homozygotes (previous study), the >10kb deletion is associated with more severe expression of FH than is the exon 3 mutation, although the plasma lipoprotein concentrations are not significantly different between the 10kb and ex3 heterozygotes. Since in homozygotes plasma cholesterol levels in 10kb are 60% higher than in ex3 patients, these observations suggest that the expression of the normal LDL-R allele compensates for the lack of a second allele in 10kb heterozygotes.

  8. Genetic polymorphism in dopamine receptor D4 is associated with early body condition in a large population of greater flamingos, Phoenicopterus roseus.

    Science.gov (United States)

    Gillingham, Mark A F; Bechet, Arnaud; Geraci, Julia; Wattier, Remi; Dubreuil, Christine; Cezilly, Frank

    2012-08-01

    Body condition is an important determinant of fitness in many natural populations. However, as for many fitness traits, the underlying genes that regulate body condition remain elusive. The dopamine receptor D4 gene (DRD4) is a promising candidate as dopamine is known to play an important role in the regulation of food intake and the metabolism of both glucose and lipids in vertebrates. In this study, we take advantage of a large data set of greater flamingos, Phoenicopterus roseus, to test whether DRD4 polymorphism predicts early body condition (EBC) while controlling for whole-genome effects of inbreeding and outbreeding using microsatellite multilocus heterozygosity (MLH). We typed 670 of these individuals for exon 3 of the homologue of the human DRD4 gene and 10 microsatellite markers. When controlling for the effects of yearly environmental variations and differences between sexes, we found strong evidence of an association between exon 3 DRD4 polymorphisms and EBC, with 2.2-2.3% of the variation being explained by DRD4 polymorphism, whereas there was only weak evidence that MLH predicts EBC. Because EBC is most likely a polygenic trait, this is a considerable amount of variation explained by a single gene. This is to our knowledge, the first study to show an association between exon 3 DRD4 polymorphism and body condition in non-human animals. We anticipate that the DRD4 gene as well as other genes coding for neurotransmitters and their receptors may play an important role in explaining variation in traits that affect fitness.

  9. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina

    Science.gov (United States)

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2016-01-01

    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5–10 μg NMDA caused 30–50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina. PMID:27611432

  10. Population-based input function modeling for [(18F]FMPEP-d 2, an inverse agonist radioligand for cannabinoid CB1 receptors: validation in clinical studies.

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    Paolo Zanotti-Fregonara

    Full Text Available BACKGROUND: Population-based input function (PBIF may be a valid alternative to full blood sampling for quantitative PET imaging. PBIF is typically validated by comparing its quantification results with those obtained via arterial sampling. However, for PBIF to be employed in actual clinical research studies, its ability to faithfully capture the whole spectrum of results must be assessed. The present study validated a PBIF for [(18F]FMPEP-d 2, a cannabinoid CB1 receptor radioligand, in healthy volunteers, and also attempted to utilize PBIF to replicate three previously published clinical studies in which the input function was acquired with arterial sampling. METHODS: The PBIF was first created and validated with data from 42 healthy volunteers. This PBIF was used to assess the retest variability of [(18F]FMPEP-d 2, and then to quantify CB1 receptors in alcoholic patients (n = 18 and chronic daily cannabis smokers (n = 29. Both groups were scanned at baseline and after 2-4 weeks of monitored drug abstinence. RESULTS: PBIF yielded accurate results in the 42 healthy subjects (average Logan-distribution volume (V T was 13.3±3.8 mL/cm(3 for full sampling and 13.2±3.8 mL/cm(3 for PBIF; R(2 = 0.8765, p<0.0001 and test-retest results were comparable to those obtained with full sampling (variability: 16%; intraclass correlation coefficient: 0.89. PBIF accurately replicated the alcoholism study, showing a widespread ∼20% reduction of CB1 receptors in alcoholic subjects, without significant change after abstinence. However, a small PBIF-V T bias of -9% was unexpectedly observed in cannabis smokers. This bias led to substantial errors, including a V T decrease in regions that had shown no downregulation in the full input function. Simulated data showed that the original findings could only have been replicated with a PBIF bias between -6% and +4%. CONCLUSIONS: Despite being initially well validated in healthy subjects, PBIF may

  11. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population.

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    Yongfeng Yang

    Full Text Available Schizophrenia (SZ is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively. Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035, as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10(-8, respectively. After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10(-7. In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849-rs12319804-rs10845851, CC (rs12582848-rs7952915, and AAGAC (rs2041986-rs11055665-rs7314376-rs7297101-rs2098469, had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively. In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively. In conclusion, our study provides novel evidence for an association between GRIN2B

  12. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

    Science.gov (United States)

    Zhang, Hongxing; Yang, Ge; Wang, Xiujuan; Ding, Minli; Jiang, Tianzi; Lv, Luxian

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between

  13. Association between vitamin D receptor ApaI and TaqI gene polymorphisms and gestational diabetes mellitus in an Iranian pregnant women population.

    Science.gov (United States)

    Rahmannezhad, Golzar; Mashayekhi, Farideh Jalali; Goodarzi, Mohammad Taghi; Rezvanfar, Mohammad Reza; Sadeghi, Abdorrahim

    2016-04-25

    It has been proposed that variants of the nuclear vitamin D receptor (VDR) gene are associated with a susceptibility to type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Our study was aimed to evaluate a possible association between the VDR ApaI (rs7975232) and TaqI (rs731236) gene polymorphisms and susceptibility to GDM in an Iranian pregnant women population. This case-control study was performed on a population of pregnant Iranian women, including 157 GDM and 157 non-GDM subjects.VDR ApaI and TaqI polymorphisms were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Our finding showed that the genotypes frequency of VDR ApaI polymorphism was significantly different between GDM and non-GDM groups (χ(2)=8.5, P=0.014). The CC genotype increased the risk of GDM as compared to the AA genotype (AA vs.CC, OR=2.996, 95% CI=1.278-7.022, P=0.012). The genotype and allele frequencies of VDR TaqI polymorphism were significantly different between GDM and non-GDM subjects (χ(2)=7.27, P=0.026, χ(2)=4.08, P=0.043 respectively). A significant protection was shown against GDM in VDR TaqI genotypes and allele (TT vs.TC, OR=0.523, 95% CI=0.23-0.84, P=0.007, TT vs. TC+CC, OR=0.546, 95% CI=0.35-0.86, P=0.009, T vs. C, OR=0.711, 95% CI=0.511-0.99, P=0.043). In conclusion, our findings show a significant association between VDR ApaI and TaqI gene polymorphisms and the GDM at the investigated loci.

  14. No association between the TaqI A1 RFLP of the D2 receptor gene and alcoholism in a Mexican population

    Energy Technology Data Exchange (ETDEWEB)

    Cruz-Fuentes, C.; Carmarena, B.; Eroza, V. [and others

    1994-09-01

    The suggested association of the A1 allele of the D2 dopamine receptor (DRD2) human gene with alcoholism was studied by comparing the DRD2/TaqI genotypes of 36 healthy controls and 38 individuals who met the DSM-III-R diagnostic criteria for alcohol dependence. All subjects were unrelated, with parents and grandparents of Mexican origin. The alcoholics in our sample suffered one of the following conditions: delirium tremens (16.6%), alcohol hallucinosis (56.6%) or uncomplicated alcohol withdrawal (26.4%). Eight-eight percent of the controls carried the A1 allele. The frequency of the DRD2 A1 allele in the Mexican urban sample (pA1 = 0.61) was 2 to 3-fold higher than reported in Caucasian populations from the USA and Europe, but similar to the allele frequencies found in defined Amerindian populations. There were not significant differences in the prevalence or allele frequency between alcoholics (pA1 = 0.64) and controls, regardless if the alcoholics were subtyped accordingly to severity, age of onset or positive family history. Alcoholics had higher scores than controls in the neuroticism (N) and psychoticism (P) subscales on the Eysenck personality test: alcoholics P = 6.2 {+-} 2.9, N = 16.0 {+-} 4.2 vs. controls P = 2.5 {+-} 2.3, N = 5.7 {+-} 5.1; p<0.001 and p<0.001, respectively. However, no relationship between personality traits and genotypes was found. Our results do not support a consistent association between the TaqI A1 RFLP for the DRD2 gene and alcoholism.

  15. Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex.

    Science.gov (United States)

    Freund, M; Walther, T; von Bohlen Und Halbach, O

    2014-02-01

    Aside from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a G protein-coupled receptor being essential for angiotensin-(1-7) signaling. Mas is not only expressed in the periphery but also within the brain, e.g. in the dentate gyrus (DG) and the piriform cortex (PC). Since the DG is capable of adult neurogenesis, we examined the impact of a deletion of Mas upon adult neurogenesis. Deletion of Mas did not alter cell proliferation in the adult DG (as monitored with phosphohistone H3) and did not alter cell death (as monitored with activated Caspase 3). However, Mas deficiency resulted in an increase in the number of doublecortin (DCX) positive cells, indicating that lack of Mas increases the number of this cell population. Concerning the PC, it is discussed whether adult neurogenesis occurs under physiological conditions in this area. We could demonstrate that Mas deficiency has an impact on cell division and on the population of DCX-positive cells within the PC. Since Mas is not expressed before birth within the brain, our data may suggest that adult hippocampal neurogenesis and neurogenesis occurring during prenatal development share several common mechanisms, but are, at least in part, differentially regulated. Moreover, since deficiency for Mas increases the numbers of DCX-positive young neurons, blockage of Mas might be beneficial in stimulating neurogenesis in adults.

  16. Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity.

    Science.gov (United States)

    Nogueiras, Ruben; Pérez-Tilve, Diego; Veyrat-Durebex, Christelle; Morgan, Donald A; Varela, Luis; Haynes, William G; Patterson, James T; Disse, Emmanuel; Pfluger, Paul T; López, Miguel; Woods, Stephen C; DiMarchi, Richard; Diéguez, Carlos; Rahmouni, Kamal; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H

    2009-05-06

    We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.

  17. Regulation of pregnane-X-receptor, CYP3A and P-glycoprotein genes in the PCB-resistant killifish (Fundulus heteroclitus) population from New Bedford Harbor

    Energy Technology Data Exchange (ETDEWEB)

    Gräns, Johanna; Wassmur, Britt; Fernández-Santoscoy, María [Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg (Sweden); Zanette, Juliano; Woodin, Bruce R.; Karchner, Sibel I. [Biology Department, MS #32, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Nacci, Diane E.; Champlin, Denise; Jayaraman, Saro [Office of Research and Development, National Health and Environmental Effects Research Laboratory, Atlantic Ecology Division, United States Environmental Protection Agency, 27 Tarzwell Drive, Narragansett, RI 02882 (United States); Hahn, Mark E.; Stegeman, John J. [Biology Department, MS #32, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Celander, Malin C., E-mail: malin.celander@gu.se [Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg (Sweden)

    2015-02-15

    Highlights: • Basal levels of PXR and Pgp mRNA are lower in liver of fish from NBH than from SC. • Hepatic PXR, CYP3A and Pgp mRNA levels are induced by PCB in fish from NBH. • Both non-dioxin-like and dioxin-like PCBs induce PXR, CYP3A and Pgp in NBH fish. • Branchial PXR and CYP3A mRNA levels are induced by PCB 126 in fish from SC. • There is possible cross-talk between AhR and PXR signaling in killifish. - Abstract: Killifish survive and reproduce in the New Bedford Harbor (NBH) in Massachusetts (MA), USA, a site severely contaminated with polychlorinated biphenyls (PCBs) for decades. Levels of 22 different PCB congeners were analyzed in liver from killifish collected in 2008. Concentrations of dioxin-like PCBs in liver of NBH killifish were ∼400 times higher, and the levels of non-dioxin-like PCBs ∼3000 times higher than in killifish from a reference site, Scorton Creek (SC), MA. The NBH killifish are known to be resistant to the toxicity of dioxin-like compounds and to have a reduced aryl hydrocarbon receptor (AhR) signaling response. Little is known about the responses of these fish to non-dioxin-like PCBs, which are at extraordinarily high levels in NBH fish. In mammals, some non-dioxin-like PCB congeners act through nuclear receptor 1I2, the pregnane-X-receptor (PXR). To explore this pathway in killifish, a PXR cDNA was sequenced and its molecular phylogenetic relationship to other vertebrate PXRs was determined. Killifish were also collected in 2009 from NBH and SC, and after four months in the laboratory they were injected with a single dose of either the dioxin-like PCB 126 (an AhR agonist) or the non-dioxin-like PCB 153 (a mammalian PXR agonist). Gills and liver were sampled three days after injection and transcript levels of genes encoding PXR, cytochrome P450 3A (CYP3A), P-glycoprotein (Pgp), AhR2 and cytochrome P450 1A (CYP1A) were measured by quantitative PCR. As expected, there was little effect of PCB exposure on mRNA expression of

  18. Regulation of pregnane-X-receptor, CYP3A and P-glycoprotein genes in the PCB-resistant killifish (Fundulus heteroclitus) population from New Bedford Harbor.

    Science.gov (United States)

    Gräns, Johanna; Wassmur, Britt; Fernández-Santoscoy, María; Zanette, Juliano; Woodin, Bruce R; Karchner, Sibel I; Nacci, Diane E; Champlin, Denise; Jayaraman, Saro; Hahn, Mark E; Stegeman, John J; Celander, Malin C

    2015-02-01

    Killifish survive and reproduce in the New Bedford Harbor (NBH) in Massachusetts (MA), USA, a site severely contaminated with polychlorinated biphenyls (PCBs) for decades. Levels of 22 different PCB congeners were analyzed in liver from killifish collected in 2008. Concentrations of dioxin-like PCBs in liver of NBH killifish were ∼400 times higher, and the levels of non-dioxin-like PCBs ∼3000 times higher than in killifish from a reference site, Scorton Creek (SC), MA. The NBH killifish are known to be resistant to the toxicity of dioxin-like compounds and to have a reduced aryl hydrocarbon receptor (AhR) signaling response. Little is known about the responses of these fish to non-dioxin-like PCBs, which are at extraordinarily high levels in NBH fish. In mammals, some non-dioxin-like PCB congeners act through nuclear receptor 1I2, the pregnane-X-receptor (PXR). To explore this pathway in killifish, a PXR cDNA was sequenced and its molecular phylogenetic relationship to other vertebrate PXRs was determined. Killifish were also collected in 2009 from NBH and SC, and after four months in the laboratory they were injected with a single dose of either the dioxin-like PCB 126 (an AhR agonist) or the non-dioxin-like PCB 153 (a mammalian PXR agonist). Gills and liver were sampled three days after injection and transcript levels of genes encoding PXR, cytochrome P450 3A (CYP3A), P-glycoprotein (Pgp), AhR2 and cytochrome P450 1A (CYP1A) were measured by quantitative PCR. As expected, there was little effect of PCB exposure on mRNA expression of AhR2 or CYP1A in liver and gills of NBH fish. In NBH fish, but not in SC fish, there was increased mRNA expression of hepatic PXR, CYP3A and Pgp upon exposure to either of the two PCB congeners. However, basal PXR and Pgp mRNA levels in liver of NBH fish were significantly lower than in SC fish. A different pattern was seen in gills, where there were no differences in basal mRNA expression of these genes between the two

  19. Leptin Receptor Gene Gln223Arg Polymorphism Is Not Associated with Hypertension: A Preliminary Population-Based Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Geórgia das Graças Pena

    2014-01-01

    Full Text Available Hypertension is responsible for high morbidity and mortality as one of the most important cardiometabolic risk factors. The aim of the study was to investigate whether the Gln223Arg in the leptin receptor (LEPR influences the prevalence of hypertension. A cross-sectional study was carried out in individuals aged ≥ 18 years. Polymorphism identification was performed using PCR-RFLP analysis. Participants with blood pressure ≥ 140/90 mmHg or medication use were considered hypertensive. Frequencies, means, cross-tabulations, and multivariate models were produced to study differences in hypertension prevalence by genotypes. The study includes 470 participants. The frequency of GG polymorphism variant was 10.43%, 46.81% AG, and 42.77% AA. The distribution of hypertension frequency by LEPR genotypes was the following: AA 43.8%, AG 40.4%, and GG 40.8%; there were no significant differences between groups. Comparative analysis which used multivariate Poisson regression adjusted by many potential confounders (age, sex, schooling, smoking, alcohol intake, obesity, and family history of parental obesity did not modify this result. In this large sample of population-based study, the association of the LEPR Gln223Arg gene polymorphism with hypertension was not observed.

  20. Associations of Toll-like receptor 7 and 8 Polymorphisms with Asthma and Asthma-related Phenotypes in a Chinese Han Population.

    Science.gov (United States)

    Zhang, Qian; Qian, Fen-Hong; Yin, Xiao-Wei; Cao, Qi; Bai, Jian-Ling; Du, Qiang; Shi, Yi

    2015-12-01

    Toll-like receptor (TLR) 7 and 8 mediate anti-virus immunity and are of particular relevance to asthma. However, very little information about genetic association on TLR7/8 and asthma are available. This study aimed to evaluate the effects of polymorphisms in TLR7 and 8 on asthma risk and asthma-related phenotypes in a Chinese Han population. We enrolled 462 unrelated adult asthmatic patients and 398 healthy volunteers. The genotypes of tagging single nucleotide polymorphisms (SNPs) in TLR7 and 8 genes were determined using multiplex SNaPshot SNP genotyping assay. We used case-control and case-only studies to assess any links with asthma and asthma-related phenotypes. There was no association between the variants in TLR7 and 8 and asthma susceptibility. However, our results revealed that the genetic variants in TLR7 and 8 were associated with asthma-related phenotypes, including eosinophil counts, serum immunoglobulin E levels, lung function, and asthma severity as well. Our study suggests that TLR7 and 8 polymorphisms may play a considerable role in the pathogenesis of asthma. It will help in better understanding the pathogenesis of asthma and development of more effective strategies for asthma prevention, prediction, and therapy.

  1. Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-/sup 3/H-dihydroalprenolol binding

    Energy Technology Data Exchange (ETDEWEB)

    Brodde, O.E.; Leifert, F.J.; Krehl, H.J.

    1982-01-01

    We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-/sup 3/H-dihydroalprenolol ((-)-/sup 3/H-DHA) binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-/sup 3/H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors.

  2. Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

    Science.gov (United States)

    Ramos-Lopez, Omar; Panduro, Arturo; Martinez-Lopez, Erika; Roman, Sonia

    2016-01-01

    Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG. PMID:26907331

  3. Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

    Science.gov (United States)

    Majid, Misbah; Masood, Akbar; Kadla, Showkat Ahmad; Hameed, Iqra; Ganai, Bashir A

    2017-02-01

    Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P 2; 95 % CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ (2) = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

  4. The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Valdimara Corrêa Vieira

    2011-06-01

    Full Text Available Polymorphisms in genes that encode chemokines or their receptors can modulate susceptibility to human immunodeficiency virus (HIV infection and disease progression. The objective of this study was to assess the frequency of polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A and their role in the course of HIV infection in a Southern Brazilian population. Clinical data were obtained from 249 patients for an average period of 6.4 years and genotypes were determined by standard polymerase chain reaction (PCR and PCR-restriction fragment length polymorphism. Survival analyses were conducted for three outcomes: CD4+ T-cell counts below 200 cells/µL, acquired immune deficiency syndrome (AIDS or death. The frequency of the polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A were 0.024, 0.113, 0.487 and 0.207, respectively. CCR5-Δ32 was associated with a reduction in the risk for CD4+ T-cell depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was associated with a reduction in the risk for developing AIDS. SDF1-3'A was also associated with decreased risk for AIDS, but its effect was only evident when CCR2-64I was present as well. These results highlight the possibility of using these markers as indicators for the prognosis of disease progression and provide evidence for the importance of analysing the effects of gene polymorphisms in a combined fashion.

  5. Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

    Directory of Open Access Journals (Sweden)

    Omar Ramos-Lopez

    2016-02-01

    Full Text Available Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG. This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively. Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively. In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG.

  6. Association Study of a Proliferation-inducing Ligand, Spermatogenesis Associated 8, Platelet-derived Growth Factor Receptor-alpha, and POLB Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population

    OpenAIRE

    Ping Li; Yuan Li; Ai-Hong Zhou; Si Chen; Jing Li; Xiao-Ting Wen; Zi-Yan Wu; Liu-Bing Li; Feng-Chun Zhang; Yong-Zhe Li

    2016-01-01

    Background: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. This study was conducted to examine whether the association of a proliferation-inducing ligand (APRIL), spermatogenesis associated 8 (SPATA8), platelet-derived growth factor receptor-alpha (PDGFRA), and DNA polymerase beta (POLB) with SLE can be replicated in a Chinese Han population. Methods: Chinese SLE patients (n = 1247) and ethnically and geographically matched healthy cont...

  7. Studies of membrane fluidity and heart contractile force in Trypanosoma cruzi infected mice

    Directory of Open Access Journals (Sweden)

    Julio E Enders

    2004-11-01

    Full Text Available In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250 were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01. The density (expressed as fmol/mg.prot of the receptors was similar to non-infected mice (71.96 ± 0.36 in both the acute (78.24 ± 1.67 and indeterminate phases (77.28 ± 0.91, but lower in the chronic disease (53.32 ± 0.71. Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.

  8. GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz; Radomska, Katarzyna J;

    2015-01-01

    of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells...

  9. Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men.

    Science.gov (United States)

    Stich, Vladimir; Pelikanova, Tereza; Wohl, Petr; Sengenès, Coralie; Zakaroff-Girard, Alexia; Lafontan, Max; Berlan, Michel

    2003-09-01

    The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.

  10. Glycyrrhetic acid synergistically enhances β₂-adrenergic receptor-Gs signaling by changing the location of Gαs in lipid rafts.

    Directory of Open Access Journals (Sweden)

    Qian Shi

    Full Text Available Glycyrrhetic acid (GA exerts synergistic anti-asthmatic effects via a β₂-adrenergic receptor (β₂AR-mediated pathway. Cholesterol is an important component of the structure and function of lipid rafts, which play critical roles in the β₂AR-Gs-adenylate cyclase (AC-mediated signaling pathway. Owing to the structural similarities between GA and cholesterol, we investigated the possibility that GA enhances β₂AR signaling by altering cholesterol distribution. Azide-terminal GA (ATGA was synthesized and applied to human embryonic kidney 293 (HEK293 cells expressing fusion β₂AR, and the electron spin resonance (ESR technique was utilized. GA was determined to be localized predominantly on membrane and decreased their cholesterol contents. Thus, the fluidity of the hydrophobic region increased but not the polar surface of the cell membrane. The conformations of membrane proteins were also changed. GA further changed the localization of Gαs from lipid rafts to non-raft regions, resulting the binding of β₂AR and Gαs, as well as in reduced β₂AR internalization. Co-localization of β₂AR, Gαs, and AC increased isoproterenol-induced cAMP production and cholesterol reloading attenuated this effect. A speculation wherein GA enhances beta-adrenergic activity by increasing the functional linkage between the subcomponents of the membrane β₂AR-protein kinase A (PKA signaling pathway was proposed. The enhanced efficacy of β₂AR agonists by this novel mechanism could prevent tachyphylaxis.

  11. Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

    Institute of Scientific and Technical Information of China (English)

    Rile Hu; Shigang Zhao; Guangming Niu; Chunyu Zhang; Zhiguang Wang; Mingfang Jiang

    2006-01-01

    BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population.OBJECTIVE: To analyze the association between the polymorphism of beta1 adrenergic receptor (β1-AR)gene G1165C (Arg389Gly), an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population.DESIGN: A cross-sectional study.SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society.PARTICIPANTS: The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure: ① Normal blood pressure group (n=117): systolic blood pressure (SBP) < 140 mm Hg (1 mm Hg =0.133 kPa), diastolic blood pressure (DBP) < 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group (n=122): including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation.METHODS: The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Peripheral venous blood (5 mL) was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR G1165C (Gly389Arg) genotype were detected with the Sequenom system

  12. Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bendtsen, Flemming; Gerbes, A L

    1992-01-01

    The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial...

  13. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens Henrik

    2001-01-01

    ) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P controls 1.01 ml/mmHg; P ... systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P blood pressure (-6%; P blood flow (-22%; P ... with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis....

  14. Beta-adrenergic stimulation reverses the I Kr-I Ks dominant pattern during cardiac action potential.

    Science.gov (United States)

    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T; Chen-Izu, Ye

    2014-11-01

    β-Adrenergic stimulation differentially modulates different K(+) channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of I Ks, I Kr, and I K1 currents in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K(+) current to the total repolarization reserve. In this study, we used an innovative AP-clamp sequential dissection technique to directly record the dynamic I Ks, I Kr, and I K1 currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of I Ks, I Kr, and I K1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca(2+) homeostasis. We found that isoproterenol treatment significantly enhanced I Ks, moderately increased I K1, but slightly decreased I Kr in a dose-dependent manner. The dominance pattern of the K(+) currents was I Kr > I K1 > I Ks at the control condition, but reversed to I Kr < I K1 < I Ks following β-adrenergic stimulation. We systematically determined the changes in the relative contribution of I Ks, I Kr, and I K1 to cardiac repolarization during AP at different adrenergic states. In conclusion, the β-adrenergic stimulation fine-tunes the cardiac AP morphology by shifting the power of different K(+) currents in a dose-dependent manner. This knowledge is important for designing antiarrhythmic drug strategies to treat hearts exposed to various sympathetic tones.

  15. Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Bendtsen, F; Gerbes, A L

    1992-01-01

    The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial...... natriuretic factor. Arterial norepinephrine level, an index of overall sympathetic nervous activity (3.08 nmol/L in patients vs. 1.36 nmol/L in controls; p blood volume (mean = 23 ml/kg in patients vs. 27 ml/kg in controls; p ....05). Similarly, renal venous norepinephrine level (an index of renal sympathetic tone; 4.26 nmol/L in patients vs. 1.78 nmol/L in controls; p blood volume (r = -0.53, n = 18, p

  16. [Modulation of the beta-adrenergic system during acute myocardial infarction: rationale for a new clinical trial].

    Science.gov (United States)

    Ibáñez, Borja; Fuster, Valentín; Macaya, Carlos; Jiménez-Borreguero, Jesús; Iñiguez, Andrés; Fernández-Ortiz, Antonio; Sanz, Ginés; Sánchez-Brunete, Vicente

    2011-07-01

    Acute myocardial infarction is caused by sudden coronary artery occlusion. Persistent ischemia results in necrosis of the myocardial tissue supplied by the occluded vessel. It has recently been shown that the final size of the infarct is a major predictor of future clinical events, and is, therefore, used as a surrogate outcome in clinical trials. Moreover, it has become clear that the duration of ischemia in the main determinant of the success of myocardial salvage (i.e. of non-necrotic at-risk myocardium). In addition to minimizing the time between symptom onset and reperfusion, there is considerable interest in finding therapies that can further limit the size of the infarction (i.e. cardioprotective therapies) and they are the focus of numerous clinical studies. Oral β-blockade within the first few hours of an AMI is a class-IA indication in clinical practice guidelines. However, early intravenous β-blockade, even before coronary artery reperfusion, is not routinely recommended. Preclinical research has demonstrated that the selectiveβ1-blocker metoprolol is able to reduce the infarct size only when administered before coronary artery reperfusion, which indicates that its cardioprotective properties are secondary to its ability to reduce reperfusion injury. In addition, retrospective studies of AMI suggest that starting intravenous β-blockade early has clinical benefits (i.e. lower mortality and better recovery of left ventricular contractility) in patients without contraindications. Our general hypothesis is that early administration of metoprolol (i.e. intravenously before reperfusion) results in smaller infarcts than administering the drug orally after reperfusion. The Effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion (METOCARD-CNIC) trial will test this hypothesis in patients with ST-segment elevation AMI.

  17. Corticosterone time-dependently modulates {beta}-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus.

    NARCIS (Netherlands)

    Pu, Z.; Krugers, H.; Joëls, M.

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining

  18. Beta-adrenergic activation of solute coupled water uptake by toad skin epithelium results in near-isosmotic transport

    DEFF Research Database (Denmark)

    Nielsen, Robert; Larsen, Erik Hviid

    2007-01-01

    (V) decreased to 0.50+/-0.15 nL cm(-2) x s(-1), which is significantly different from zero. Isoproterenol decreased the osmotic concentration of the transported fluid, C(osm) approximately 2 x I(SC)(Eqv)/J(V), from 351+/-72 to 227+/-28 mOsm (Ringer's solution: 252.8 mOsm). J(V) depicted a saturating function......(V) with a [Na+] of the transported fluid of 130+/-24 mM ([Na+]Ringer's solution = 117.4 mM). Addition of bumetanide to the inside solution reduced J(V). Water was transported uphill and J(V) reversed at an excess outside osmotic concentration, deltaC(S,rev) = 28.9+/-3.9 mOsm, amiloride decreased delta......Transepithelial potential (V(T)), conductance (G(T)), and water flow (J(V)) were measured simultaneously with good time resolution (min) in isolated toad (Bufo bufo) skin epithelium with Ringer on both sides. Inside application of 5 microM isoproterenol resulted in the fast increase in G(T) from 1...

  19. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Wang, Xianshu; Fredericksen, Zachary S

    2010-01-01

    ) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases...... associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR...

  20. Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes.

    Science.gov (United States)

    Molina, Cristina E; Llach, Anna; Herraiz-Martínez, Adela; Tarifa, Carmen; Barriga, Montserrat; Wiegerinck, Rob F; Fernandes, Jacqueline; Cabello, Nuria; Vallmitjana, Alex; Benitéz, Raúl; Montiel, José; Cinca, Juan; Hove-Madsen, Leif

    2016-01-01

    Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation.

  1. Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Bjerre, Karsten; Giobbie-Hurder, Anita;

    2012-01-01

    Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker...

  2. Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study

    DEFF Research Database (Denmark)

    Schutte, Aletta E; Myburgh, Anélda; Olsen, Michael Hecht;

    2012-01-01

    INTRODUCTION: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the...

  3. Analysis of adrenergic regulation of melatonin synthesis in Siberian hamster pineal emphasizes the role of HIOMT.

    Science.gov (United States)

    Ceinos, R M; Chansard, M; Revel, F; Calgari, C; Míguez, J M; Simonneaux, V

    2004-01-01

    Seasonal variations of environmental factors are translated into annual fluctuations in synthesis and release of melatonin, which in turn acts as a neuroendocrine messenger for the synchronization of annual functions. So far, most studies performed to understand the regulation of melatonin synthesis have used the non seasonal laboratory rat. It was demonstrated that nocturnal melatonin synthesis depends on alpha- and beta-adrenergic activation of the enzyme arylalkylamine N-acetyltransferase (AA-NAT). In this study, we investigated the mechanisms of melatonin synthesis in the Siberian hamster, a seasonal species with marked photoperiodic variation in melatonin peak duration and amplitude. A beta-adrenergic receptor agonist alone markedly stimulated AA-NAT activity and melatonin synthesis and release. An alpha-adrenergic receptor agonist, while having no effect per se, potentiated the beta-adrenergic stimulation of AA-NAT activity both in vitro and in vivo. Strikingly, the potentiation of AA-NAT activity did not result in a potentiation of melatonin synthesis, suggesting that the rate of melatonin production is limited downstream in the metabolic pathway, most probably at the level of hydroxyindole-O-methyltransferase (HIOMT). HIOMT presented a constitutively high activity that was not acutely (within hours) stimulated by beta-adrenergic agonist, but was rather up-regulated by chronic application of the agonist. This long-term beta-adrenergic regulation may explain the reported large photoperiodic variation of HIOMT activity that drives the photoperiodic variation in melatonin peak.

  4. Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11- hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India

    Indian Academy of Sciences (India)

    Manisha Patnaik; Pallabi Pati; Surendra N. Swain; Manoj K. Mohapatra; Bhagirathi Dwibedi; Shantanu K. Kar; Manoranjan Ranjit

    2014-12-01

    Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.

  5. Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11- hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India

    Indian Academy of Sciences (India)

    Manisha Patnaik; Pallabi Pati; Surendra N. Swain; Manoj K. Mohapatra; Bhagirathi Dwibedi; Shantanu K. Kar; Manoranjan Ranjit

    2015-06-01

    Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.

  6. Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking

    OpenAIRE

    Nicola Pirastu; Maarten Kooyman; Michela Traglia; Antonietta Robino; Willems, Sara M.; Giorgio Pistis; Pio D'Adamo; Najaf Amin; Angela d'Eustacchio; Luciano Navarini; Cinzia Sala; Lennart C. Karssen; Cornelia van Duijn; Daniela Toniolo; Paolo Gasparini

    2014-01-01

    textabstractCoffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 peopl...

  7. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia.

    Science.gov (United States)

    Bhuvanendran, Saatheeyavaane; Hussin, Hani M; Meran, Lila P; Anthony, Amy A; Zhang, Leilei; Burch, Lauranell H; Phua, Kia K; Ismail, Asma; Balaram, Prabha

    2011-09-01

    Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p = 0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p population and suggests that these polymorphisms confer a higher risk for typhoid, infection. The higher incidence of typhoid fever in Kelantan could be attributed to the higher percentage of Malays (95%) in this state. In order to reduce the incidence of this disease, people with these polymorphisms, can be prioritised for prophylactic strategies.

  8. Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population

    Indian Academy of Sciences (India)

    Abdul Haseeb; Mohammad Iliyas; Subhabrata Chakrabarti; Arif A Farooqui; Sudhir R Naik; Sudip Ghosh; Madhuri Suragani; Nasreen Z Ehtesham

    2009-09-01

    Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South Indian population ( = 699) for a possible association of these polymorphisms with the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin ( = 0.017). Furthermore, C1431T was associated with resistin in different tertiles. Prevalence of the ‘Pro-C’ haplotype decreased with increasing tertiles of resistin (84.1% to 75.4%, = 0.037). Plasma resistin levels were not found to be associated with MS and type 2 diabetes. These results point to a likely association of plasma resistin levels with PPAR polymorphisms in the Indian population.

  9. Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentine population.

    Science.gov (United States)

    Cédola, Maia; Chiani, Yosena; Pretre, Gabriela; Alberdi, Lucrecia; Vanasco, Bibiana; Gómez, Ricardo M

    2015-06-01

    Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in the recognition of and subsequent immune response activation against leptospirosis in humans. The genetic polymorphism in TLR2 of an arginine to glutamine substitution at residue 753 (Arg753Gln) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to Leptospira spp. This bacterium signals through TLR2/TLR1 heterodimers in human cells. The aim of the present study was to investigate the Arg753Gln single-nucleotide polymorphism (SNP) of the TLR2 gene, and the isoleucine to serine transversion at position 602 (Ile602Ser) of the TLR1 gene (previously associated with Lyme disease), in leptospirosis patients compared to healthy controls, carrying out a retrospective case/control study. The TLR2 polymorphism adenine (A) allele was observed in 7.3% of leptospirosis patients but was not found in the control group, whereas the guanine (G) allele of the TLR1 polymorphism was found in 63.6% of patients and 41.6% of controls. Susceptibility to leptospirosis disease was increased 10.57-fold for carriers of the TLR2 G/A genotype (P=0.0493) and 3.85-fold for carriers of the TLR1 G/G genotype (P=0.0428). Furthermore, the risk of developing hepatic insufficiency and jaundice was increased 18.86- and 27.60-fold for TLR2 G/A carriers, respectively. Similarly, the risk of developing jaundice was increased 12.67-fold for TLR1 G allele carriers (G/G and T/G genotypes). In conclusion, the present data suggest that the TLR2 Arg753Gln and TLR1 Ile602Ser SNPs influence the risk of developing leptospirosis and its severity.

  10. Fracture risk in perimenopausal women treated with beta-blockers

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha

    2004-01-01

    beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

  11. NCBI nr-aa BLAST: CBRC-GGAL-22-0004 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-22-0004 sp|P07700|ADRB1_MELGA Beta-1 adrenergic receptor (Beta-1 adrenoceptor) (Beta-...1 adrenoreceptor) (Beta-T) gb|AAA49627.1| beta-adrenergic receptor P07700 1e-123 60% ...

  12. NCBI nr-aa BLAST: CBRC-TNIG-02-0011 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TNIG-02-0011 sp|P07700|ADRB1_MELGA Beta-1 adrenergic receptor (Beta-1 adrenoceptor) (Beta-...1 adrenoreceptor) (Beta-T) gb|AAA49627.1| beta-adrenergic receptor P07700 1e-138 61% ...

  13. NCBI nr-aa BLAST: CBRC-ACAR-01-0606 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0606 sp|P07700|ADRB1_MELGA Beta-1 adrenergic receptor (Beta-1 adrenoceptor) (Beta...-1 adrenoreceptor) (Beta-T) gb|AAA49627.1| beta-adrenergic receptor P07700 1e-119 59% ...

  14. Association of a Common Oxytocin Receptor Gene Polymorphism with Self-Reported ‘Empathic Concern’ in a Large Population of Healthy Volunteers

    Science.gov (United States)

    Reinders, Anette; Siffert, Doris; Stelmach, Patrick; Knop, Dietmar; Horn, Peter Alexander; Siffert, Winfried

    2016-01-01

    Background Previous research has linked genomic variations of the oxytocin receptor (OXTR) gene with individual differences in empathy. The impact of these variations on specific cognitive and emotional aspects of empathy, however, remains to be clarified. Methods We analysed associations of a common OXTR polymorphism (rs53576) with trait empathy in a sample of 421 blood donors (231 M, 190 F; age 18–74) using the Interpersonal Reactivity Index (IRI) as an established multidimensional self-report measure of empathy. Results Female sex was significantly associated with higher empathy scores in all IRI scales (pOXTR gene polymorphism with trait empathy and especially with emotional aspects of empathy. This association is possibly weaker or absent in men compared to women. PMID:27467763

  15. A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Hansen, Bettina; Troldborg, Anne;

    2014-01-01

    BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA...... according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations...... in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory...

  16. Impact of the -1438G>a polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk: a case-control study in a Spanish Mediterranean population.

    Science.gov (United States)

    Sorlí, José V; Francés, Francesc; González, José I; Guillén, Marisa; Portolés, Olga; Sabater, Antonio; Coltell, Oscar; Corella, Dolores

    2008-01-01

    Research into the genetic factors that regulate food intake is arousing great interest. The polymorphism -1438G>A in the serotonin 2A receptor or 5-hydroxytriptamine (5-HT) type 2A receptor (5-HTR2A) gene has been associated with alterations in food intake such as anorexia and bulimia. However, its association with obesity has not been studied to the same extent. Our aim, therefore, was to estimate the association between the -1438G>A polymorphism and obesity risk and related anthropometric variables in a Spanish Mediterranean population. A case-control study including 303 cases and 606 controls paired by gender and age was undertaken. The association between the -1438G>A polymorphism and obesity and other anthropometric measures was studied. No association with obesity risk was observed. However, when only the obese group was analyzed, it was observed that AA subjects presented a lower body mass index (BMI) than G allele carriers (35.2+/-5.3 kg/m2 vs 37.5+/-7.8 kg/m2; P=0.039). Moreover, significant differences were also obtained in waist perimeter that was lower in AA subjects compared to G allele carriers (105+/-11 cm vs 112+/-17 cm; P=0.011). In conclusion, although the -1438G>A polymorphism is not a relevant marker for obesity risk, this variant may play a role in determining BMI in obese subjects.

  17. Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population

    Directory of Open Access Journals (Sweden)

    Habiba Al-Safar

    2015-01-01

    Full Text Available Background. Transcription factor 7-like 2 gene (TCF7L2 and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2 have a profound effect on the incidence of type 2 diabetes mellitus (T2DM and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282 of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2 and rs1801282 (PPAR-γ2 P12A variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], P=0.017, but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96 was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population.

  18. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  19. Adrenergic effects on secretion of amylase from the rat salivary glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1988-01-01

    The present study was undertaken to investigate the effect of adrenergic agents on secretion of amylase from the salivary glands in vivo. Saliva was collected from the distal oesophagus in conscious rats. Adrenaline increased the concentration of amylase in saliva and serum significantly....... The result of infusion of alpha- and beta-adrenergic antagonists as well as noradrenaline and isoproterenol showed that secretion of salivary amylase is predominantly mediated by stimulation of beta-adrenergic receptors, especially of the beta 1-subtype. Investigation of the isoenzyme pattern in saliva......, pancreatic juice and serum demonstrated that the major component in serum is salivary amylase. This study has shown that beta-adrenergic agents stimulate secretion of amylase from the salivary glands in rats. Though the secretion is mainly exocrine small amounts of amylase is found in serum, which seems...

  20. Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Feng He

    2014-04-01

    Full Text Available Left main coronary artery disease (LMCAD is a particular severe phenotype of coronary artery disease (CAD and heritability. Interleukin (IL may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD. In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS and ligation detection reaction (LDR method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR = 1.46, 95% confidence interval (CI = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037. None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

  1. Family-based association study of interleukin 6 (IL6) and its receptor (IL6R) functional polymorphisms in schizophrenia in the Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Permoda-Osip, Agnieszka; Twarowska-Hauser, Joanna

    2015-08-15

    Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. Recent studies indicate a role of excessive interleukin-6 (IL6) signaling in the pathogenesis of schizophrenia. Findings regarding changes in the circulating levels of soluble interleukin-6 receptor (sIL6R) in schizophrenia have been equivocal. The study was performed on a group of 147 trio (patients diagnosed with schizophrenia and their healthy parents). Polymorphisms of IL6 (rs1800795, rs1800797) and IL6R (rs4537545, rs4845617, rs2228145) genes were genotyped with the use of TaqMan SNP Genotyping Assays. No association of the polymorphisms from IL6 and IL6R genes with schizophrenia was found. We also investigated haplotypes in IL6 gene (consisting of rs1800795 and rs1800797) and in IL6R gene (consisting of rs4537545, rs2228145). We also found no preference in transmission of any haplotype. Our results do not support the theory that polymorphisms of IL6 and IL6R genes are involved in the pathogenesis of schizophrenia. It seems advisable to carry out further examinations of the role of these polymorphisms in schizophrenia by means of TDT method and classical (case-control) association method.

  2. Immediate post-defeat infusions of the noradrenergic receptor antagonist propranolol impair the consolidation of conditioned defeat in male Syrian hamsters.

    Science.gov (United States)

    Gray, Cloe Luckett; Krebs-Kraft, Desiree L; Solomon, Matia B; Norvelle, Alisa; Parent, Marise B; Huhman, Kim L

    2015-12-01

    Social defeat occurs when an animal is attacked and subjugated by an aggressive conspecific. Following social defeat, male Syrian hamsters fail to display species-typical territorial aggression and instead exhibit submissive or defensive behaviors even when in the presence of a non-aggressive intruder. We have termed this phenomenon conditioned defeat (CD). The mechanisms underlying CD are not fully understood, but data from our lab suggest that at least some of the mechanisms are similar to those that mediate classical fear conditioning. The goal of the present experiment was to test the hypothesis that noradrenergic signaling promotes the consolidation of CD, as in classical fear conditioning, by determining whether CD is disrupted by post-training blockade of noradrenergic activity. In Experiment 1, we determined whether systemic infusions of the noradrenergic receptor antagonist propranolol (0, 1.0, 10, or 20mg/kg) given immediately after a 15 min defeat by a resident aggressor would impair CD tested 48 h later. Hamsters that were given immediate post-training infusions of propranolol (1.0, but not 10 or 20mg/kg) showed significantly less submissive behavior than did those given vehicle infusions supporting the hypothesis that there is noradrenergic modulation of the consolidation of a social defeat experience. In Experiment 2, we demonstrated that propranolol (1.0mg/kg) given immediately, but not 4 or 24h, after defeat impaired CD tested 48 h after defeat indicating that the window within which the memory for social defeat is susceptible to beta-adrenergic modulation is temporary. In Experiment 3, we examined whether central blockade of noradrenergic receptors could recapitulate the effect of systemic injections by giving an intracerebroventricular infusion of propranolol immediately after defeat and examining the effect on CD 24h later. Centrally administered propranolol (20 μg/3 μl but not 2 μg/3 μl) was also effective in dose-dependently reducing

  3. TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet’s Disease in Turkish Population

    Directory of Open Access Journals (Sweden)

    Gaye Erten

    2016-01-01

    Full Text Available Objectives. In our study we aimed to determine VDR gene polymorphisms in patients with Behçet’s disease (BD and neuro-Behçet’s disease (NBD in Turkish population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB, and 30 healthy controls were investigated. Genomic DNA was extracted from whole blood using the QIAamp Blood Kit. VDR ApaI (rs7975232, VDR FokI (rs2228570, and VDR TaqI (rs731236 genotyping was performed by real-time polymerase chain reaction with SimpleProbe melting-curve analysis. Results. The allelic and genotype distributions of FokI and TaqI polymorphisms were not different among Behçet’s disease, neuro-Behçet’s disease, and control subjects in Turkish population (p>0.05. Only the frequency of ApaI A allele in control is higher than that in BD (60% versus 38.5%, and the p value is 0.014, but the power is not enough to conclude that ApaI A allele is protective in BD in our study. Taken together, we found no significant differences between the BD, NBD, and control groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles frequencies. Conclusions. Future studies with larger patients’ numbers may show differences between VDR polymorphisms and Behçet’s disease.

  4. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

    DEFF Research Database (Denmark)

    Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K

    2010-01-01

    regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta......-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1...

  5. Dopamine receptor D2 and catechol-O-methyltransferase gene polymorphisms associated with anorexia nervosa in Chinese Han population: DRD2 and COMT gene polymorphisms were associated with AN.

    Science.gov (United States)

    Peng, Sufang; Yu, Shunying; Wang, Qian; Kang, Qing; Zhang, Yanxia; Zhang, Ran; Jiang, Wenhui; Qian, Yiping; Zhang, Haiyin; Zhang, Mingdao; Xiao, Zeping; Chen, Jue

    2016-03-11

    Dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) are important in dopamine system which is proved to be associated with food-anticipatory behavior, food restriction, reward and motivation. This has made them good candidates for anorexia nervosa (AN). The aim of this work is to explore the roles of DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) gene polymorphisms in the susceptibility of AN within the Chinese Han population. We recruited 260AN patients with DSM-IV diagnosis criteria, and 247 unrelated, normal weight controls. DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) were genotyped in all subjects. We found rs1800497 and rs4633 were associated with the susceptibility of AN within the Chinese Han sample, and allele C of rs1800497 was a protective factor. There was a gene-gene interaction between rs1800497 of DRD2 gene and rs4633 of COMT gene. We concluded that rs1800497 and rs4633 play important roles in the AN susceptibility with respect to the Chinese Han population. The gene-gene interaction between DRD2 and COMT contributes to the risk of AN.

  6. Anatomically heterogeneous populations of CB1 cannabinoid receptor-expressing interneurons in the CA3 region of the hippocampus show homogeneous input-output characteristics.

    Science.gov (United States)

    Szabó, Gergely G; Papp, Orsolya I; Máté, Zoltán; Szabó, Gábor; Hájos, Norbert

    2014-12-01

    A subpopulation of GABAergic cells in cortical structures expresses CB1 cannabinoid receptors (CB1 ) on their axon terminals. To understand the function of these interneurons in information processing, it is necessary to uncover how they are embedded into neuronal circuits. Therefore, the proportion of GABAergic terminals expressing CB1 and the morphological and electrophysiological properties of CB1 -immunoreactive interneurons should be revealed. We investigated the ratio and the origin of CB1 -expressing inhibitory boutons in the CA3 region of the hippocampus. Using immunocytochemical techniques, we estimated that ∼40% of GABAergic axon terminals in different layers of CA3 also expressed CB1 . To identify the inhibitory cell types expressing CB1 in this region, we recorded and intracellularly labeled interneurons in hippocampal slices. CB1 -expressing interneurons showed distinct axonal arborization, and were classified as basket cells, mossy-fiber-associated cells, dendritic-layer-innervating cells or perforant-path-associated cells. In each morphological category, a substantial variability in axonal projection was observed. In contrast to the diverse morphology, the active and passive membrane properties were found to be rather similar. Using paired recordings, we found that pyramidal cells displayed large and fast unitary postsynaptic currents in response to activating basket and mossy-fiber-associated cells, while they showed slower and smaller synaptic events in pairs originating from interneurons that innervate the dendritic layer, which may be due to dendritic filtering. In addition, CB1 activation significantly reduced the amplitude of the postsynaptic currents in each cell pair tested. Our data suggest that CB1 -expressing interneurons with different axonal projections have comparable physiological characteristics, contributing to a similar proportion of GABAergic inputs along the somato-dendritic axis of CA3 pyramidal cells.

  7. Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: Role of serine protease inhibitor Kazal 1type and alcohol

    Institute of Scientific and Technical Information of China (English)

    Venkata Muddana; David C Whitcomb; Janette Lamb; Julia B Greer; Beth Elinoff; Robert H Hawes; Peter B cotton; Michelle A Anderson; Randall E Brand; Adam Slivka

    2008-01-01

    AIM: To test the hypothesis that calcium sensing receptor (CASR) polymorphisms are associated with chronic pancreatitis (CP), and to determine whether serine protease inhibitor Kazal 1type (SPfNK1) N34S or alcohol are necessary co-factors in its etiology.METHODS: Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SP/NK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisrns (SNPs) in exon 7 (A986S, R990G, and Q1011E).RESULTS: The CASR exon 7 R990G polymorphism was significantly associated with CP (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015). The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption (OR,3.12; 95% CI, 1.14-9.13; P = 0.018). There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected.CONCLUSION: Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.

  8. Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

    Science.gov (United States)

    Mehta, Prachi; Premkumar, Brian; Morris, Renée

    2016-08-03

    The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions.

  9. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia Expresion aberrante de receptores de glucagón en tejido adrenal de un paciente con síndrome de Cushing e hiperplasia adrenal macronodular indedependiente de ACTH

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar

  10. Polymorphism of adiponectin (45T/G) and adiponectin receptor-2 (795G/A) in an Iranian population: relation with insulin resistance and response to treatment with pioglitazone in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hosein

    2012-05-01

    Adiponectin, an adipose-derived plasma protein, is reduced in patients with obesity and type 2 diabetes. Thiazolidinediones can increase adiponectin levels and improve insulin sensitivity. This study investigated the associations between type 2 diabetes and two single-nucleotide polymorphisms in the adiponectin (45T/G) and adiponectin receptor-2 gene (795G/A), and investigated whether these genetic variants affect the response to pioglitazone in Iranian patients with type 2 diabetes. We genotyped 128 non-diabetic participants and 101 patients with type 2 diabetes for 45T/G and 795G/A with polymerase chain reaction-restriction fragment length polymorphism assays. Patients were treated with pioglitazone for 12 weeks, after which we compared laboratory parameters in these two groups. Fasting blood sugar differed significantly in individuals with different 795G/A genotypes after pioglitazone treatment (P = 0.009). The mean decrease in insulin/glucose ratio after treatment also differed significantly in individuals with different 45T/G genotypes (P = 0.035). The T allele frequency for 45T/G was 87.11% in controls versus 81.68% in patients (P = 0.071). The TG and GG genotypes were more frequent in patients (P = 0.032). The G allele frequency for 795G/A was 76.17% in controls versus 80.20% in patients (P = 0.179). 795G/A variants were not significantly different between patient and control group. The adiponectin gene 45T/G mutation may be an important determinant of type 2 diabetes in the Iranian population. However, adiponectin 45T/G and adiponectin receptor-2 795G/A polymorphisms were not significantly associated with the response to pioglitazone in our sample.

  11. No consistent effect of ADRB2 haplotypes on obesity, hypertension and quantitative traits of body fatness and blood pressure among 6,514 adult Danes

    DEFF Research Database (Denmark)

    Gjesing, Anette P; Sparsø, Thomas; Borch-Johnsen, Knut;

    2009-01-01

    BACKGROUND: Evidence regarding the association of variation within ADRB2, the gene encoding the beta-adrenergic receptor 2 (ADRB2) with obesity and hypertension is exceedingly ambiguous. Despite negative reports, functional impacts of individual genetic variants have been reported. Also, functional...... prevalence of obesity and hypertension among adults. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped five variants required to capture common variation in a region including the ADRB2 locus in a population-based study of 6,514 unrelated, middle-aged Danes. Phases of the genotypes were estimated in silico....... The variations were then investigated for their combined association with obesity, hypertension and related quantitative traits. The present study did not find consistent evidence for an association of ADRB2 variants with either obesity or hypertension when variations were analysed in a case-control study...

  12. A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective

    DEFF Research Database (Denmark)

    Hommer, A.; Wickstrom, J.; Friis, M.M.

    2008-01-01

    , time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices......OBJECTIVE: To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prostaglandin analogues bimatoprost, travoprost, and latanoprost as fixed-combination therapies with timolol, a beta-adrenergic receptor antagonist. METHODS: A decision analytic cost...... inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months. RESULTS: The analysis showed that fixed...

  13. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette;

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing......In 1972, Brazeau et al. isolated somatostatin (somatotropin release-inhibiting factor, SRIF), a cyclic polypeptide with two biologically active isoforms (SRIF-14 and SRIF-28). This event prompted the successful quest for SRIF receptors. Then, nearly a quarter of a century later, it was announced...... that a neuropeptide, to be named cortistatin (CST), had been cloned, bearing strong resemblance to SRIF. Evidence of special CST receptors never emerged, however. CST rather competed with both SRIF isoforms for specific receptor binding. And binding to the known subtypes with affinities in the nanomolar range, it has...

  14. Intrahippocampal Infusions of Anisomycin Produce Amnesia: Contribution of Increased Release of Norepinephrine, Dopamine, and Acetylcholine

    Science.gov (United States)

    Qi, Zhenghan; Gold, Paul E.

    2009-01-01

    Intra-amygdala injections of anisomycin produce large increases in the release of norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment with intra-amygdala injections of the beta-adrenergic receptor antagonist propranolol attenuates anisomycin-induced amnesia without reversing the inhibition of protein synthesis, and…

  15. Effects of beta-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis

    NARCIS (Netherlands)

    van der Drift, S. G. A.; Everts, R. R.; Houweling, M.; van Leengoed, L. A. M. G.; Stegeman, J. A.; Tielens, A. G. M.; Jorritsma, R.

    2013-01-01

    An in vitro model was used to investigate effects of beta-hydroxybutyrate and isoproterenol (beta-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n = 5) and cows with clinical ketosis (n =3). Incubation with 3.0 mmol/L beta-hydroxyb

  16. Limited Efficacy of Propranolol on the Reconsolidation of Fear Memories

    Science.gov (United States)

    Muravieva, Elizaveta V.; Alberini, Cristina M.

    2010-01-01

    Previous studies suggested that the beta-adrenergic receptor antagonist propranolol might be a novel, potential treatment for post-traumatic stress disorder (PTSD). This hypothesis stemmed mainly from rodent studies showing that propranolol interferes with the reconsolidation of Pavlovian fear conditioning (FC). However, subsequent investigations…

  17. NCBI nr-aa BLAST: CBRC-TTRU-01-0013 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-0013 ref|XP_974214.1| PREDICTED: similar to beta adrenergic receptor [Tribolium... castaneum] gb|EFA10769.1| hypothetical protein TcasGA2_TC012597 [Tribolium castaneum] XP_974214.1 1e-125 66% ...

  18. Hypoxia, hormones, and red blood cell function in chick embryos.

    Science.gov (United States)

    Dragon, Stefanie; Baumann, Rosemarie

    2003-04-01

    The red blood cell function of avian embryos is regulated by cAMP. Adenosine A(2A) and beta-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO(2) transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

  19. Hypertension after clonidine withdrawal.

    Science.gov (United States)

    Husserl, F E; deCarvalho, J G; Batson, H M; Frohlich, E D

    1978-05-01

    Rebound hypertension occurred in two patients upon clonidine withdrawal. Treatment of the hypertensive crisis consists of both alpha- and beta-adrenergic receptor blockade, reserpine, or the reintroduction of clonidine. With effective control of pressure during the crisis, long-term antihypertensive therapy must be resumed.

  20. Using Propranolol to Block Memory Reconsolidation in Female Veterans with PTSD

    Science.gov (United States)

    2015-11-01

    memory reconsolidation, such that lower levels of estrogen should be related to greater reconsolidation. The role of estrogen in facilitating ...Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors. Journal of Neuroscience, 19, 6623...events. Further preliminary evidence indicates that gonadal hormones help regulate the extinction of fear responses, as women in late follicular

  1. The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

    Directory of Open Access Journals (Sweden)

    Lázaro Rafael

    2009-11-01

    Full Text Available Abstract Background The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1 has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. Methods We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. Results The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005. No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023, but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Conclusion Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.

  2. Association between peroxisome proliferator-activated receptor-γcoactivator-1α gene polymorphisms and type 2 diabetes in southern Chinese population: role of altered interaction with myocyte enhancer factor 2C

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shao-ling; LU Wen-sheng; YAN Li; WU Mu-chao; XU Ming-tong; CHEN Li-hong; CHENG Hua

    2007-01-01

    Background Some single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-Y coactivator (PGC)-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1a and type 2 diabetes in the southern Chinese population and to determine whether the common variants: Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor (MEF) 2C.Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Thereafter, 263 type 2diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C.Results Three frequent SNPs (Thr394Thr, Gly482Ser and Thr528Thr) were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls (40.1% vs 29.3%, P<0.01). Even in controls, the 482Ser(A) carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly(G) carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr (A) had a synergic effect on the interaction between

  3. Relación del polimorfismo TaqI del gen del receptor de la vitamina D con la lepra lepromatosa en población mexicana Association between the TaqI polymorphism of Vitamin D Receptor gene and lepromatous leprosy in a Mexican population sample

    Directory of Open Access Journals (Sweden)

    Jesús Salvador Velarde Félix

    2009-02-01

    Full Text Available OBJETIVO: Determinar la relación del polimorfismo TaqI del gen del receptor de la vitamina D (RVD con la lepra lepromatosa (LL en individuos originarios de Sinaloa, México. MATERIAL Y MÉTODOS: Se amplificó un fragmento de 740 pb del gen RVD en muestras de ADN de 71 pacientes con LL y 144 controles en el Hospital General de Culiacán durante el periodo 2004-2007. El polimorfismo se identificó mediante la endonucleasa TaqI. RESULTADOS: Se observó un aumento de relevancia estadística del genotipo TT en pacientes con LL en comparación con los controles (p= 0.040; RM= 1.82. CONCLUSIÓN: Se demuestra un nexo entre el genotipo TT y la susceptibilidad a la LL.OBJETIVE: To establish the association of the vitamin D receptor gene TaqI polymorphism with lepromatous leprosy (LL in individuals from Sinaloa, Mexico. MATERIAL AND METHODS: A 740 bp fragment was amplified from the VDR gene in DNA samples of 71 patients with LL and 144 controls in the Hospital General de Culiacán during 2004-2007. Polymorphism was identified through TaqI endonuclease. RESULTS: A significant increase in the genotype TT of the VDR gene was observed in patients when compared to controls (p = 0.040; OR = 1.82. CONCLUSIONS: Our data support the association between the TT genotype and susceptibility to LL in this Mexican population.

  4. Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    FANG Yu; ZHANG Lu; ZHOU Gang-qiao; WANG Zhi-fu; ZENG Zhao-shu; LUO Zhi-yi; LI Lei; LIU Bao-chi

    2011-01-01

    Background The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAKI) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population. Methods Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database.They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status,Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and primary diseases. Results rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46;95% confidence interval (Cl), 1.12-26.67; P=0.018), and such associations were also observed between the IRAK1variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% Cl, 1.05-2.70; P=0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95%Cl, 1.13-4.94; P=0.02) when compared with the wild haplotype. This association was not significant in male patients. Conclusions The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate

  5. 中国肥胖患者β_2 肾上腺素受体基因多态性的研究%Polymorphism in β_2 Adrenergic Receptor Gene in Chinese Population with Obesity

    Institute of Scientific and Technical Information of China (English)

    吴红梅; 白怀; 范平; 刘瑞; 刘宇; 刘秉文

    2009-01-01

    Objective To investigate the variation of β_2 adrenergic receptor (β_2AR) gene and its association with obesity in Chinese population. Methods The allele of β_2AR gene at Argl6Gly and Gln27Glu sites were analysed with polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in 396 people with Han nationality in Chengdu, among whom 126 had obesity. Results The allele frequencies of Arg and Gly at Argl6Gly site were 0. 571 and 0. 429 for the obese people, and 0. 559 and 0. 441 for the non-obese people, respectively. The allele frequencies of Gin and Glu at Gln27Glu site were 0. 920 and 0. 080 for the obese people, and 0. 916 and 0. 084 for the non-obese people, respectively. No significant differences were found in the genotype frequencies of the two sites between non-obese and obese people. The non-obese females and obese males with genotype Arg/Arg at Argl6Gly site had elevated serum TC and LDL-C levels compared with those who carried Arg/ Gly or Gly/Gly (P0.05).在Arg16Gly位点,非肥胖组女性和肥胖组男性Arg/Arg基因型携带者血清 TC 和 LDLC 水平分别高于Arg/Gly和Gly/Gly基因型携带者(P0.05).结论 β_2AR基因Arg16Gly和Gln27Glu多态性与成都地区中国汉族人肥胖无关联,但Arg16Gly位点对特定性别非肥胖及肥胖人群血清TC、LDLC及部分载脂蛋白水平有一定影响.

  6. Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI expression in liver and association with lipid levels in a population-based study

    Directory of Open Access Journals (Sweden)

    Barrett-Connor Elizabeth

    2010-01-01

    Full Text Available Abstract Background Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. Methods We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII expression in 91 human liver tissues using quantitative real-time PCR. Results Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4 and triglycerides (p = 1.3 × 10-3 and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4. These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women Conclusions Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

  7. Genetic diversity of the IL-4, IL-4 receptor and IL-13 loci in mestizos in the general population and in patients with asthma from three subpopulations in Mexico.

    Science.gov (United States)

    López, K I M; Martínez, S E F; Moguel, M C M; Romero, L T; Figueroa, C S; Pacheco, G V; Ibarra, B; Corona, J S

    2007-02-01

    Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype.

  8. Study of polymorphisms in the interleukin-4 and IL-4 receptor genes in a population of Brazilian patients with multiple sclerosis Estudo de polimorfismos nos genes da interleucina-4 (*33C-T e receptor IL-4 (*Q551R numa população de pacientes brasileiros com esclerose múltipla

    Directory of Open Access Journals (Sweden)

    Thereza Quirico-Santos

    2007-03-01

    Full Text Available This study aimed to investigate in a population of Brazilian patients with multiple sclerosis (MS single-nucleotide polymorphisms (SNP in the promoter region of IL4 (*33C-T and receptor IL4R (*Q551R A-G genes proposed to interfere with disease progression. No significant differences were observed in either of the SNPs investigated between healthy controls (n=135 and MS patients (n=129. However, the IL4+33 TT genotype was significantly (p=0.039 higher in African descendants MS (AF-MS= 9.09% than in Caucasian MS (CA-MS= 1.35%. It was also observed a significant (p=0.016 increase for the IL4R* Q551R CC genotype in AF-MS compared to those of Caucasian ethnicity (AF-MS= 21.62%; CA-MS= 4.35%. These results suggest that IL4+33 and IL4R*Q551 polymorphisms may have a disease-promoting role of TH2 mediators in African MS descendants. Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.Este é um estudo inédito realizado numa população brasileira de pacientes portadores de esclerose múltipla (EM visando determinar uma possível associação na expressão de polimorfismo (SNP nos genes da citocina reguladora IL4 (*33C-T e do seu respectivo receptor IL4R (*Q551R A-G capazes de modificar a evolução da doença. Não foi observada diferença significativa em ambos SNPs analisados entre o grupo controle de indivíduos saudáveis (n=135 e os pacientes com EM (n=129. Contudo, o genotipo IL4+33 TT apresentava percentual mais elevado (9,09% nos pacientes EM com descendência africana (AF-EM do que nos descendentes caucasianos (CA-EM=1,35% sendo esta diferença significativa (p=0,039. Também foi observado um aumento significativo (p=0,016 para o genotipo IL4R* Q551R CC nos pacientes AF-EM (21,62% comparando-se com CA-EM (4,35%. Estes resultados indicam que polimorfismos nos genes da citocina IL4 (*33C-T e respectivo receptor IL4R

  9. Expression of TGF-beta superfamily growth factors, their receptors, the associated SMADs and antagonists in five isolated size-matched populations of pre-antral follicles from normal human ovaries

    DEFF Research Database (Denmark)

    Kristensen, Stine Gry; Andersen, Kasper; Clement, Christian Alexandro;

    2014-01-01

    proteins/genes were analysed by immunocytochemistry and quantitative RT-PCR.TGF-β superfamily genes with overall highest mRNA expressions levels included growth differentiation factors 9 (GDF9), bone morphogenic protein-15 (BMP15), BMP6, BMP-receptor-2 (BMPR2), anti-Müllerian hormone receptor 2 (AMHR2...

  10. Propranolol.

    Science.gov (United States)

    Bailey, Debra S.; Praderio, Nestor H.

    1994-01-01

    Research indicates that the beta-adrenergic blocking agent propranolol has been used effectively in the treatment of aggressive behavior in diverse populations of both children and adults with and without organic diagnoses. The literature is reviewed and some of the current proposed explanations for propranolol's antiaggressive effect are…

  11. Trace amine-associated receptors are olfactory receptors in vertebrates.

    Science.gov (United States)

    Liberles, Stephen D

    2009-07-01

    The mammalian nose is a powerful chemosensor, capable of detecting and distinguishing a myriad of chemicals. Sensory neurons in the olfactory epithelium contain two types of chemosensory G protein-coupled receptors (GPCRs): odorant receptors (ORs), which are encoded by the largest gene family in mammals, and trace amine-associated receptors (TAARs), a smaller family of receptors distantly related to biogenic amine receptors. Do TAARs play a specialized role in olfaction distinct from that of ORs? Genes encoding TAARs are found in diverse vertebrates, from fish to mice to humans. Like OR genes, each Taar gene defines a unique population of canonical sensory neurons dispersed in a single zone of the olfactory epithelium. Ligands for mouse TAARs include a number of volatile amines, several of which are natural constituents of mouse urine, a rich source of rodent social cues. One chemical, 2-phenylethylamine, is reported to be enriched in the urine of stressed animals, and two others, trimethylamine and isoamylamine, are enriched in male versus female urine. Furthermore, isoamylamine has been proposed to be a pheromone that induces puberty acceleration in young female mice. These data raise the possibility that some TAARs are pheromone receptors in the nose, a hypothesis consistent with recent data suggesting that the olfactory epithelium contains dedicated pheromone receptors, separate from pheromone receptors in the vomeronasal organ. Future experiments will clarify the roles of TAARs in olfaction.

  12. Differences in beta-adrenergic regulation of cyclic AMP formation in cerebral cortical slices of the rat and spiny mouse--Acomys cahirinus.

    Science.gov (United States)

    Chalecka-Franaszek, E; Nalepa, I; Vetulani, J

    1990-01-01

    In both the rat and Acomys cahirinus the adrenergic cyclic AMP generating system in the brain is dependent not only on beta-, but also on alpha-adrenoceptors. The relative role of alpha-adrenoceptors is much greater in the Acomys cahirinus. This feature makes the Acomys an interesting animal model for investigating the role of alpha-beta-adrenoceptor coupling in generation of cyclic AMP and the mechanism of action of antidepressant treatment.

  13. sup 86 Rb(K) influx and ( sup 3 H)ouabain binding by human platelets: Evidence for beta-adrenergic stimulation of Na-K ATPase activity

    Energy Technology Data Exchange (ETDEWEB)

    Turaihi, K.; Khokher, M.A.; Barradas, M.A.; Mikhailidis, D.P.; Dandona, P. (Royal Free Hospital and School of Medicine, London (England))

    1989-08-01

    Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), {sup 86}Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific ({sup 3}H)ouabain binding by the human platelet. This {sup 86}Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active {sup 86}Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active {sup 86}Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets.

  14. Sympathetic reflex control of skeletal muscle blood flow in patients with congestive heart failure: evidence for beta-adrenergic circulatory control

    Energy Technology Data Exchange (ETDEWEB)

    Kassis, E.; Jacobsen, T.N.; Mogensen, F.; Amtorp, O.

    1986-11-01

    Mechanisms controlling forearm muscle vascular resistance (FMVR) during postural changes were investigated in seven patients with severe congestive heart failure (CHF) and in seven control subjects with unimpaired left ventricular function. Relative brachioradial muscle blood flow was determined by the local /sup 133/Xe-washout technique. Unloading of baroreceptors with use of 45 degree upright tilt was comparably obtained in the patients with CHF and control subjects. Control subjects had substantially increased FMVR and heart rate to maintain arterial pressure whereas patients with CHF had decreased FMVR by 51 +/- 11% and had no increase in heart rate despite a fall in arterial pressure during upright tilt. The autoregulatory and local vasoconstrictor reflex responsiveness during postural changes in forearm vascular pressures were intact in both groups. In the patients with CHF, the left axillary nerve plexus was blocked by local anesthesia. No alterations in forearm vascular pressures were observed. This blockade preserved the local regulation of FMVR but reversed the vasodilator response to upright tilt as FMVR increased by 30 +/- 7% (p less than .02). Blockade of central neural impulses to this limb combined with brachial arterial infusions of phentolamine completely abolished the humoral vasoconstriction in the tilted position. Infusions of propranolol to the contralateral brachial artery that did not affect baseline values of heart rate, arterial pressure, or the local reflex regulation of FMVR reversed the abnormal vasodilator response to upright tilt as FMVR increased by 42 +/- 12% (p less than .02). Despite augmented baseline values, forearm venous but not arterial plasma levels of epinephrine increased in the tilted position, as did arteri rather than venous plasma concentrations of norepinephrine in these patients.

  15. [Effects of tilt test and beta-adrenergic stimulation on the QT interval in normal children and pediatric patients with unexplained syncope].

    Science.gov (United States)

    Arnaiz, Pilar; Dumas, Eduardo; Heusser, Felipe; González, Rolando; Jalil, Jorge

    2004-02-01

    In normal children, any procedure that increases heart rate, such as the tilt test, may shorten the QT interval. The effect of the tilt test on QT interval in children with syncope remains unknown. We analyzed the response of RR and QT intervals during a tilt test in 3 groups of children: 28 healthy children (group 1), 26 with syncope of unknown etiology and negative tilt test results (group 2), and 17 with vasovagal syncope (group 3). During the tilt test, RR and QT intervals were significantly shortened in groups 1 and 2. In group 3, RR interval was lengthened during syncope whereas the QT interval remained constant. QT interval lengthening during the tilt test is not a characteristic finding in normal children or in children with vasovagal syncope.

  16. Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Liu, Xiaoqiu; Li, Fengying; Sun, Shu Qiang; Thangavel, Muthusamy; Kaminsky, Joseph; Balazs, Louisa; Ostrom, Rennolds S

    2010-06-01

    Pulmonary fibroblasts regulate extracellular matrix production and degradation and are critical in maintenance of lung structure, function, and repair, but they also play a central role in lung fibrosis. cAMP-elevating agents inhibit cytokine- and growth factor-stimulated myofibroblast differentiation and collagen synthesis in pulmonary fibroblasts. In the present study, we overexpressed adenylyl cyclase 6 (AC6) in pulmonary fibroblasts and measured cAMP production and collagen synthesis. AC6 overexpression enhanced cAMP production and the inhibition of collagen synthesis mediated by isoproterenol and beraprost, but not the responses to butaprost or PGE(2). To examine if increased AC6 expression would impact the development of fibrosis in an animal model, we generated transgenic mice that overexpress AC6 under a fibroblast-specific promoter, FTS1. Lung fibrosis was induced in FTS1-AC6(+/-) mice and littermate controls by intratracheal instillation of saline or bleomycin. Wild-type mice treated with bleomycin showed extensive peribronchial and interstitial fibrosis and collagen deposition. By contrast, FTS1-AC6(+/-) mice displayed decreased fibrotic development, lymphocyte infiltration (as determined by pathological scoring), and lung collagen content. Thus, AC6 overexpression inhibits fibrogenesis in the lung by reducing pulmonary fibroblast-mediated collagen synthesis and myofibroblast differentiation. Because AC6 overexpression does not lead to enhanced basal or PGE(2)-stimulated levels of cAMP, we conclude that endogenous catecholamines or prostacyclin is produced during bleomycin-induced lung fibrosis and that these signals have antifibrotic potential.

  17. Melatonin responses to clonidine and yohimbine challenges.

    OpenAIRE

    Kennedy, S.H.; Gnam, W; Ralevski, E; Brown, G. M.

    1995-01-01

    Melatonin (MT) release from the pineal gland has been used as a marker for central noradrenergic function in major depression. Norepinephrine acts at both alpha and beta adrenergic receptors on the pinealocyte membrane to mediate nocturnal MT release, but in humans the contribution of each receptor class is unclear. In order to explore the effect of alpha 2 receptors on MT release, 10 female subjects were given oral challenges, in separate placebo-controlled trials, of either 10.8 mg of yohim...

  18. A Pharmacological Primer of Biased Agonism

    OpenAIRE

    Andresen, Bradley T.

    2011-01-01

    Biased agonism is one of the fastest growing topics in G protein-coupled receptor pharmacology; moreover, biased agonists are used in the clinic today: carvedilol (Coreg®) is a biased agonist of beta-adrenergic receptors. However, there is a general lack of understanding of biased agonism when compared to traditional pharmacological terminology. Therefore, this review is designed to provide a basic introduction to classical pharmacology as well as G protein-coupled receptor signal transductio...

  19. Opioid Receptors.

    Science.gov (United States)

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  20. Counting Populations

    Science.gov (United States)

    Damonte, Kathleen

    2004-01-01

    Scientists use sampling to get an estimate of things they cannot easily count. A population is made up of all the organisms of one species living together in one place at the same time. All of the people living together in one town are considered a population. All of the grasshoppers living in a field are a population. Scientists keep track of the…

  1. Contributions by the CAG-repeat Polymorphism of the Androgen Receptor Gene and Circulating Androgens to Muscle Size. Odense Androgen Study - A Population-based Study of 20-29 Year-old Danish Men

    DEFF Research Database (Denmark)

    Nielsen, Torben Leo; Hagen, Claus; Wraae, Kristian;

    2007-01-01

    Context: The number of CAG-repeats within the CAG-repeat polymorphism of the androgen receptor gene is inversely correlated with the transcriptional activity of the androgen receptor. Objective: To study the effect of the CAG-repeat number and circulating androgens on muscle size, to examine......-repeat number correlated inversely with thigh and axial muscle area and with lower and upper extremity lean body mass. Except for upper extremity lean body mass, these findings remained significant in multivariate analyses controlling for circulating androgens, physical activity, smoking, alcohol intake...

  2. Role of beta2 agonists in respiratory medicine with particular attention to novel patents and effects on endocrine system and immune response.

    Science.gov (United States)

    Larocca, Nancy E; Moreno, Dolores; Garmendia, Jenny V; De Sanctis, Juan B

    2011-09-01

    Beta adrenergic receptors are very important in respiratory medicine. Traditionally, the stimulation of beta adrenergic receptors by beta2-agonists is commonly used for giving bronchodilation in chronic airflow obstruction However; the wide distribution of these receptors in cells and tissues other than airway smooth muscle suggests that beta agonists should offer other beneficial effects in respiratory disease. Recent studies have shown the importance of these receptors in the modulation of endocrine and immune system that affect respiratory function and may decrease therapy effectiveness in asthma and chronic obstructive pulmonary disease. New patented compound and uses have provided new insights in future therapeutics of respiratory diseases in which genetic, endocrine and immune response should be considered.

  3. Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.

    Science.gov (United States)

    Weisbrod, C J; Minson, C T; Joyner, M J; Halliwill, J R

    2001-12-01

    1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 85%) in eight healthy men and women (18-26 years) after selective alpha-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after phentolamine (compared to +16.8 +/- 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by approximately 50%, but dilatation was still present (+24.7 +/- 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 +/- 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional alpha-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by beta-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

  4. Promoting Population

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    THE world's population reached 5 billion in 1987,then 6 billion in 1999;now,in 2011,it is 7 billion.For a country with a set birth control policy,the way in which Chinese people and the media view this number has greatly changed.People are increasingly reflecting on the concept of population from a more scientific and rational perspective.This shift is a change from how people perceived population in the past.

  5. Dopamine-induced cyclic AMP increase in canine myocardium, kidney and superior mesenteric artery.

    Directory of Open Access Journals (Sweden)

    Kazuno,Hiroshi

    1982-04-01

    Full Text Available The effect of dopamine on cyclic AMP levels in tissue slices of canine myocardium and kidney, and in chopped superior mesenteric arterial wall was investigated to identify dopamine receptors. Tissues were incubated in modified Krebs-Henseleit Ringer bicarbonate solution at 37 degrees C for 20 min with test drugs, after 20-min preincubation. In the presence of 3-isobutyl-1-methylxanthine (IBMX, dopamine and apomorphine caused dose-dependent increases in cyclic AMP levels in the myocardium, kidney and superior mesenteric artery. Phentolamine significantly intensified the cyclic AMP-increasing effect of dopamine in the superior mesenteric artery, but it did not influence the cyclic AMP increase caused by dopamine or apomorphine in the myocardium and kidney. Propranolol markedly blocked the effect of dopamine on cyclic AMP levels in all tissues studied. Haloperidol slightly inhibited the effect of dopamine and completely blocked the effect of apomorphine in the myocardium and kidney. These data suggest that dopamine increases cyclic AMP levels by activating predominantly beta-adrenergic receptors and partly dopamine receptors in the canine myocardium, kidney and superior mesenteric artery. The present results also suggest that dopamine acts not only on beta-adrenergic and dopamine receptors but also on alpha-adrenergic receptors in the superior mesenteric artery. Contrary to the activation of beta-adrenergic and dopamine receptors, the activation of alpha-adrenergic receptors resulted in a decrease in cyclic AMP levels in this tissue.

  6. Cytokine-Leukotriene Receptor Interactions

    Directory of Open Access Journals (Sweden)

    Marek Rola-Pleszczynski

    2007-01-01

    Full Text Available Biochemical and pharmacological studies have identified the structure of leukotrienes, the pathways that lead to their synthesis, and the signaling events they trigger when they interact with their cognate receptors. A privileged interaction exists between these lipid mediators and another group of molecules essential for inflammation and immune modulation, namely, cytokines. Whereas leukotrienes can trigger the synthesis and release of selected cytokines in distinct cell populations, many cytokines can affect cellular responsiveness to leukotrienes by modulating leukotriene receptor expression. As we progressively begin to unravel these complex interactions, new areas of cell-cell communication and eventual therapeutic interventions will emerge.

  7. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H

    2010-01-01

    , nitric oxide overproduction, and cannabinoid receptor activation. Systolic incompetence in patients can be revealed by pharmacological or physical strain and during stressful procedures, such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. Systolic dysfunction has...... and electrophysiological abnormalities. This syndrome is termed cirrhotic cardiomyopathy. Results of experimental studies indicate the involvement of several mechanisms in the pathophysiology, such as reduced beta-adrenergic receptor signal transduction, altered transmembrane currents and electromechanical coupling...

  8. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  9. Association Study of a Proliferation-inducing Ligand, Spermatogenesis Associated 8, Platelet-derived Growth Factor Receptor-alpha, and POLB Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Ping Li

    2016-01-01

    Conclusions: Different genetic backgrounds from different ancestries and various populations may result in different genetic risk factors for SLE. We did not detect any significant association with SNPs of APRIL, SPATA8, PDGFRA, and POLB.

  10. Imaginary populations

    Directory of Open Access Journals (Sweden)

    A. Martínez–Abraín

    2010-01-01

    Full Text Available A few years ago, Camus & Lima (2002 wrote an essay to stimulate ecologists to think about how we define and use a fundamental concept in ecology: the population. They concluded, concurring with Berryman (2002, that a population is "a group of individuals of the same species that live together in an area of sufficient size to permit normal dispersal and/or migration behaviour and in which population changes are largely the results of birth and death processes". They pointed out that ecologists often forget "to acknowledge that many study units are neither natural nor even units in terms of constituting a population system", and hence claimed that we "require much more accuracy than in past decades in order to be more effective to characterize populations and predict their behaviour". They stated that this is especially necessary "in disciplines such as conservation biology or resource pest management, to avoid reaching wrong conclusions or making inappropriate decisions". As a population ecologist and conservation biologist I totally agree with these authors and, like them, I be¬lieve that greater precision and care is needed in the use and definition of ecological terms. The point I wish to stress here is that we ecologists tend to forget that when we use statistical tools to infer results from our sample to a population we work with what statisticians term "imaginary", "hypothetical" or "potential" popula¬tions. As Zar (1999 states, if our sample data consist of 40 measurements of growth rate in guinea pigs "the population about which conclusions might be drawn is the growth rates of all the guinea pigs that conceivably might have been administered the same food supplement under identical conditions". Such a population does not really exist, and hence it is considered a hypothetical or imaginary population. Compare that definition with the population concept that would be in our minds when performing such measurements. We would probably

  11. Population policy.

    Science.gov (United States)

    1987-03-01

    Participants in the Seminar on Population Policies for Top-level Policy Makers and Program Managers, meeting in Thailand during January 1987, examined the challenges now facing them regarding the implementation of fertility regulation programs in their respective countries -- Bangladesh, China, India, Indonesia, Malaysia, Nepal, Pakistan, the Philippines, the Republic of Korea, and Thailand. This Seminar was organized to coincide with the completion of an Economic and Social Commission for Asia and the Pacific (ESCAP) study investigating the impact and efficiency of family planning programs in the region. Country studies were reviewed at the Seminar along with policy issues about the status of women, incentive and disincentive programs, and socioeconomic factors affecting fertility. In Bangladesh the government recognizes population growth as its top priority problem related to the socioeconomic development of the country and is working to promote a reorientation strategy from the previous clinic-oriented to a multidimensional family welfare program. China's family planning program seeks to postpone marraige, space the births of children between 3-5 years, and promote the 1-child family. Its goal is to reduce the rate of natural increase from 12/1000 in 1978 to 5/1000 by 1985 and 0 by 2000. India's 7th Five-Year-Plan (1986-90) calls for establishing a 2-child family norm by 2000. In Indonesia the government's population policy includes reducing the rate of population growth, achieving a redistribution of the population, adjusting economic factors, and creating prosperous families. The government of Indonesia reversed its policy to reduce the population growth rate in 1984 and announced its goal of achieving a population of 70 million by 2100 in order to support mass consumption industries. It has created an income tax deduction system favoring large families and maternity benefits for women who have up to 5 children as incentives. Nepal's official policy is to

  12. [Population education].

    Science.gov (United States)

    Niang, M

    1992-12-01

    Africa has the highest population growth rate in the world (3%). It has 650 million people (about 900 million in 2000). Rapid population growth has serious consequences which, if not addressed, will be disastrous. This worrisome situation has led some governments to adopt demographic policies to slow down population growth. The UN Economic, Scientific and Cultural Organization (UNESCO) recommends that schools provide population education. Various population conferences have popularized population education in schools among African countries. UNESCO began its regional program on population education in Africa in 1969. National family life and population education (FL/PE) projects have increased from 4 in 1970 to 32 in 1990 (17 in French- and Portuguese-speaking Africa and 5 in English-speaking Africa). These projects teach students about the links between demographic problems and socioeconomic factors and contemporary culture. They aim for total development of the individual and improvement of the quality of life for the individual, family, and community. Topics covered in FL/PE are birth rate; fertility; health; and maternal, infant, and child mortality; unwanted pregnancy; illegal abortion; sexually transmitted diseases; rural-urban migration; and urbanization. Benin introduced FL/PE at all levels of its education system while Senegal, Guinea, Mauritania, and Zaire introduced it to only the primary and secondary school levels. Some countries teach FL/PE as one discipline while most countries (e.g., Senegal) have integrated it into other disciplines (e.g., geography). FL/PE should begin in primary schools because they have the most students and prepare students for middle schools, which provide FL/PE. Elementary education in Senegal is being overhauled to introduce current major problems bit by bit. Senegal also wants to incorporate FL/PE into literacy and adult education programs. Integration of FL/PE into other disciplines should be encouraged.

  13. Mestizo Population

    Directory of Open Access Journals (Sweden)

    Efraín Chavarria-Avila

    2015-01-01

    Full Text Available The polymorphisms in leptin (LEP G-2548A and leptin-receptor (LEPR Gln223Arg seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin, and leptin-receptor (sLeptin-receptor serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2±31.35 ng/mL but lower sLeptin-receptor (12.6±3.74 ng/mL levels than normal weight ones (17.6±14.62 ng/mL, 17.4±4.62 ng/mL, resp., P<0.001. Obese subjects carriers of Arg/Arg genotype had more (P=0.016 sLeptin-receptor (14.7±4.96 ng/mL and less (P=0.004 sLeptin (44.0±28.12 ng/mL levels than Gln/Gln genotype (11.0±2.92 ng/mL, 80.3±33.24 ng/mL, resp.. Body fat mass was lower (P from 0.003 to 0.045 for A/A (36.5%±6.80 or Arg/Arg (36.8%±6.82 genotypes with respect to G/G (41.3%±5.52 and G/A (41.6%±5.61 or Gln/Gln (43.7%±4.74 and Gln/Arg (41.0%±5.52 genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico.

  14. Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction

    Directory of Open Access Journals (Sweden)

    Tomohiko Sekioka

    2015-10-01

    Conclusions: CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.

  15. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H;

    2002-01-01

    The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-ass...... lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor...

  16. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  17. Autoradiographic localization of beta-adrenoreceptors in rat uterus

    Energy Technology Data Exchange (ETDEWEB)

    Tolszczuk, M.; Pelletier, G.

    1988-12-01

    The inhibitory effects of catecholamines on uterine smooth muscle are known to be mediated through beta-adrenergic receptors. To investigate further the distribution of these receptors in the rat uterus, we utilized in vitro autoradiography using ( SVI)-cyanopindolol (CYP), a specific beta-receptor ligand that has equal activity for both beta 1- and beta 2-receptor subtypes. The specificity of the labeling and the characterization of receptor subtypes in different cell types were achieved by displacement of radioligand with increasing concentrations of zinterol, a beta-adrenergic agonist with preferential affinity for the beta 2-adrenoreceptor subtype, and practolol, a beta-adrenergic antagonist that binds preferentially to the beta 1-subtype. Quantitative estimation of ligand binding was performed by densitometry. It was shown that the vast majority of beta-adrenoreceptors were of the beta 2-subtype and were found in high concentration not only in the myometrium but also in the endometrial and serosal epithelia. Specific labeling was also observed in glandular elements. These results suggest that beta-adrenoreceptors might be involved in different functions in the uterus.

  18. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  19. Recent developments in the study of opioid receptors.

    Science.gov (United States)

    Cox, Brian M

    2013-04-01

    It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes. In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs. This minireview summarizes these recent developments in our understanding of opiate receptors. Receptor function is also influenced by amino acid substitutions in the protein sequence. Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear. Recent studies have shed new light on how this SNP might influence opioid receptor function. In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.

  20. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;

    2015-01-01

    A high degree of structural heterogeneity of the GABAA receptors (GABAARs) has been revealed and is reflected in multiple receptor subtypes. The subunit composition of GABAAR subtypes is believed to determine their localization relative to the synapses and adapt their functional properties...... to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...

  1. Pharmacology of Casimiroa edulis; Part I. Blood pressure and heart rate effects in the anesthetized rat.

    Science.gov (United States)

    Magos, G A; Vidrio, H

    1991-02-01

    The effect of an alcoholic extract of seeds of Casimiroa edulis on blood pressure and heart rate was determined in rats anesthetized with pentobarbital and compared with that of histamine. The extract induced hypotension, accompanied at high doses by tachycardia. Hypotension after histamine was more transient and was not accompanied by changes in heart rate. Experiments with a variety of autonomic antagonists revealed that extract-induced hypotension was not mediated by histamine H2, muscarinic, or beta-adrenergic receptors, but involved an H1 mechanism. After H1 blockade, the depressor response was reversed to a pressor effect, mediated by alpha-adrenoceptor stimulation. The increase in heart rate was due in part to H1 and in part to beta-adrenergic receptor activation. It was suggested that imidazole derivatives could be responsible for the depressor effect observed. The pressor response could be caused by these or other components of the extract.

  2. Population dynamics

    Directory of Open Access Journals (Sweden)

    Cooch, E. G.

    2004-06-01

    Full Text Available Increases or decreases in the size of populations over space and time are, arguably, the motivation for much of pure and applied ecological research. The fundamental model for the dynamics of any population is straightforward: the net change over time in the abundance of some population is the simple difference between the number of additions (individuals entering the population minus the number of subtractions (individuals leaving the population. Of course, the precise nature of the pattern and process of these additions and subtractions is often complex, and population biology is often replete with fairly dense mathematical representations of both processes. While there is no doubt that analysis of such abstract descriptions of populations has been of considerable value in advancing our, there has often existed a palpable discomfort when the ‘beautiful math’ is faced with the often ‘ugly realities’ of empirical data. In some cases, this attempted merger is abandoned altogether, because of the paucity of ‘good empirical data’ with which the theoretician can modify and evaluate more conceptually–based models. In some cases, the lack of ‘data’ is more accurately represented as a lack of robust estimates of one or more parameters. It is in this arena that methods developed to analyze multiple encounter data from individually marked organisms has seen perhaps the greatest advances. These methods have rapidly evolved to facilitate not only estimation of one or more vital rates, critical to population modeling and analysis, but also to allow for direct estimation of both the dynamics of populations (e.g., Pradel, 1996, and factors influencing those dynamics (e.g., Nichols et al., 2000. The interconnections between the various vital rates, their estimation, and incorporation into models, was the general subject of our plenary presentation by Hal Caswell (Caswell & Fujiwara, 2004. Caswell notes that although interest has traditionally

  3. Stellar Populations

    NARCIS (Netherlands)

    Peletier, Reynier F.

    2013-01-01

    This is a summary of my lectures during the 2011 Canary Islands Winter School in Puerto de la Cruz. I give an introduction to the field of stellar populations in galaxies, and highlight some new results. Since the title of the Winter School is Secular Evolution in Galaxies I mostly concentrate on ne

  4. The Relationship between Esmolol and the Onset and Duration of Action of Succinylcholine in Patients Undergoing General or Orthopedic Surgery

    Science.gov (United States)

    1983-05-01

    of the autonomic nervous system. Only basic concepts concerning this research are provided below. Beta-adrenergic receptor antagonists ( beta blockers ). The...indicated (Abrams et al.. 1985). Beta blockers possess a number of adverse effects which may preclude their use in certain clinical situations. The...Currently available beta - blockers have elimination half-lives between 2 and 6 hours. These adverse effects, therefore, may dissipate slowly. Ultra

  5. Nociceptive Effects of Locally Treated Metoprolol

    Directory of Open Access Journals (Sweden)

    Nursima Cukadar

    2015-06-01

    Results: Metoprolol, an antagonist, significantly decreased the thermal latency and mechanical thresholds with dose and time dependent manner. However, dobutamine, an agonist, enhanced the latency and thresholds dose and time dependent. Conclusions: This results suggest that in contrast to dobutamine, locally treated metoprolol may cause hyperalgesic and allodynic actions. In addition, our results can demonstrate that peripheral beta-adrenergic receptors can play important roles in nociceptive process. [Cukurova Med J 2015; 40(2.000: 258-266

  6. GLP-1 Receptor Agonists

    Science.gov (United States)

    ... in Balance › GLP-1 Receptor Agonists Fact Sheet GLP-1 Receptor Agonists May, 2012 Download PDFs English Espanol Editors Silvio ... are too high or too low. What are GLP-1 receptor agonist medicines? GLP-1 receptor agonist medicines, also called ...

  7. Stickleback Population

    Directory of Open Access Journals (Sweden)

    Ulrika Candolin

    2012-01-01

    Full Text Available Human-induced eutrophication has increased offspring production in a population of threespine stickleback Gasterosteus aculeatus in the Baltic Sea. Here, we experimentally investigated the effects of an increased density of juveniles on behaviours that influence survival and dispersal, and, hence, population growth—habitat choice, risk taking, and foraging rate. Juveniles were allowed to choose between two habitats that differed in structural complexity, in the absence and presence of predators and conspecific juveniles. In the absence of predators or conspecifics, juveniles preferred the more complex habitat. The preference was further enhanced in the presence of a natural predator, a perch Perca fluviatilis (behind a transparent Plexiglas wall. However, an increased density of conspecifics relaxed the predator-enhanced preference for the complex habitat and increased the use of the open, more predator-exposed habitat. Foraging rate was reduced under increased perceived predation risk. These results suggest that density-dependent behaviours can cause individuals to choose suboptimal habitats where predation risk is high and foraging rate low. This could contribute to the regulation of population growth in eutrophicated areas where offspring production is high.

  8. Population aging.

    Science.gov (United States)

    1999-04-01

    This paper focuses on the impact of population aging in China, the most densely populated country in the world. Statistics indicate that by the end of 1998, 83.75 million out of the 1.248 billion Chinese people will be over 65 years old. According to the UN standards, China will soon become an aging society. The aging population poses several challenges to the country with the greatest challenge being the increasing social responsibility to care for the aged. With the undeveloped legislative framework to protect the interests of the aged and the serious drawbacks in the pension system to cater only to the income part and not the service part of the aged, China is not yet ready for the advent of aging. Violation of the rights of senior citizens is still very rampant despite enactment of the law on Protection of the Rights of the Elderly in 1996. Moreover, China is not economically ready to become an aging society. China faces this challenge by adopting a three-pronged approach to solve the problem namely: family support, establishment of nursing homes, and creating a social security framework that addresses the needs of the society suited to the Chinese condition. It is believed that with the growing economy of the country and the rising income of its people, a comprehensive social security net will be created to take care of the aged.

  9. Relationship between vitamin D receptor gene FokI polymorphism and alopecia areata in Inner Mon-golian Han population%内蒙古汉族人群维生素D受体FokI基因多态性与斑秃的关系

    Institute of Scientific and Technical Information of China (English)

    卓纳; 张满; 辛燕

    2015-01-01

    Objective:To determine the relationship between the polymorphism of vitamin D receptor gene FokI and alopecia areata in Inner Mongolia Han population. Methods:The polymorphism of vitamin D recep-tor Gene FokI sites in patients with alopecia areata (105 patients) and healthy controls (145 patients) were detected by PCR-RELP. Results:The genotype frequencies of FF, Ff and ff in patients were 0.324, 0.524, 0.152 and those in healthy controls were 0.297, 0.531, 0.172. There were no significant difference between the patients and the controls (P>0.05). Conclusion: There is no relationship between the polymorphism of vitamin D receptor FokI and alopecia areata in Inner Mongolia Han population.%目的::明确维生素D受体FokI基因多态性与内蒙古汉族人群斑秃的相关性。方法:运用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,检测105例斑秃患者与145名健康对照的维生素D受体基因FokI酶切位点的多态性。结果:病例组维生素D受体FokI的3种基因型FF、Ff、ff频率分别为0.324、0.524、0.152,对照组分别为0.297、0.531、0.172,两组间比较无显著性差异( P>0.05)。结论:维生素D受体FokI基因多态性可能与内蒙古汉族人群斑秃的发病无关。

  10. Liver X receptor α gene polymorphisms(-6A) of the patients with coronary heart disease in Han population in Jiangsu province%江苏地区汉族人群冠心病患者肝X受体基因-6A多态性

    Institute of Scientific and Technical Information of China (English)

    朱锦; 孙建辉; 白江涛; 罗光华

    2014-01-01

    目的:探讨江苏地区冠心病患者肝X受体(liver X receptor,LXR)基因-6A(rs11039155)多态性位点与冠心病遗传易感性的关系.方法:选取江苏地区冠心病患者165例,健康体检者191例作为对照.采用单荧光标记探针技术检测LXR-6A基因型.同时测定两组样本三酰甘油、总胆固醇、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖等生化指标.结果:LXR-6A(rs11039155)仅检出一种基因型,与探针完全匹配,出现一个融解峰,Tm值55.21 ℃.随机抽取22例样本进行测序,提示基因型为GG纯合子.结论:江苏地区汉族人群不存在LXR-6A(rs11039155)单核苷酸多态性位点.%Objective:To investigate the relation between-1i5A (rs12221497) and-6A (rs11039155) point mutation of liver X receptor α and the patients with coronary heart disease (CHD).Methods:The-6A polymorphism in the liver X receptor α gene were detected by using single-labeled probe technique.Plasma cholesterol,triglyceride,HDL-cholesterol,LDL-cholesterol,fasting blood glucose (FBG) were determined in 165 patients with CHD and 191 normal controls.Results:LXR-6A(rs11039155) had only one genetype.Randomly selected 22 cases of samples for gene sequencing,suggesting:genetypes of GG homozygote.Conclusion:There was no mutation in liver X receptor α gene-6A point in Han population in Jiangsu province.

  11. Relación del polimorfismo TaqI del gen del receptor de la vitamina D con la lepra lepromatosa en población mexicana Association between the TaqI polymorphism of Vitamin D Receptor gene and lepromatous leprosy in a Mexican population sample

    OpenAIRE

    Jesús Salvador Velarde Félix; Silvestre Guadalupe Cázarez Salazar; Rafael Castro Velázquez; José Guadalupe Rendón Maldonado; Héctor Rangel Villalobos

    2009-01-01

    OBJETIVO: Determinar la relación del polimorfismo TaqI del gen del receptor de la vitamina D (RVD) con la lepra lepromatosa (LL) en individuos originarios de Sinaloa, México. MATERIAL Y MÉTODOS: Se amplificó un fragmento de 740 pb del gen RVD en muestras de ADN de 71 pacientes con LL y 144 controles en el Hospital General de Culiacán durante el periodo 2004-2007. El polimorfismo se identificó mediante la endonucleasa TaqI. RESULTADOS: Se observó un aumento de relevancia estadística del genoti...

  12. Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans.

    Science.gov (United States)

    Moro, Cedric; Crampes, Francois; Sengenes, Coralie; De Glisezinski, Isabelle; Galitzky, Jean; Thalamas, Claire; Lafontan, Max; Berlan, Michel

    2004-05-01

    In humans, lipid mobilization is considered to depend mainly on sympathetic nervous system activation and catecholamine action. A contribution of ANP was hypothesized because we have previously shown that atrial natriuretic peptide (ANP) is a lipolytic agent on isolated human fat cells. Control of lipid-mobilizing mechanisms was investigated using in situ microdialysis in subcutaneous adipose tissue (SCAT) in healthy young men during two successive exercise bouts performed at 35% and 60% peak oxygen consumption (VO2max) after placebo or acute oral tertatolol (nonselective beta-antagonist) treatment. In placebo-treated subjects, infusion of propranolol in the probe (100 micromol/l) only partially reduced (40%) the increment in extracellular glycerol concentration (EGC) promoted by exercise. Moreover, oral beta-adrenergic receptor blockade did not prevent exercise-induced lipid mobilization in SCAT while exerting fat cell beta-adrenergic receptor blockade. Exercise-induced increase in plasma ANP was potently amplified by oral tertatolol. A positive correlation was found between EGC and plasma ANP levels but also between extracellular cGMP (i.e., index of ANP-mediated lipolysis) and EGC. Thus, we demonstrate that exercise-induced lipid mobilization resistant to local propranolol and lipid-mobilizing action observed under oral beta-blockade is related to the action of ANP. Oral beta-adrenergic receptor blockade, which potentiates exercise-induced ANP release by the heart, may contribute to lipid mobilization in SCAT. The potential relevance of an ANP-related lipid-mobilizing pathway is discussed.

  13. Photodegradation products of propranolol: the structures and pharmacological studies.

    Science.gov (United States)

    Uwai, Koji; Tani, Marie; Ohtake, Yosuke; Abe, Shinya; Maruko, Akiko; Chiba, Takashi; Hamaya, Yoshiro; Ohkubo, Yasuhito; Takeshita, Mitsuhiro

    2005-12-12

    Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are unstable in light should be carefully handled to protect their potency and ensure their safety. Propranolol (1), a beta-adrenergic receptor antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due to its naphthalene skeleton, this drug may be both light unstable and a photosensitizing agent. In this study, we isolated three photodegraded products of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N-formylpropranolol (4). The structures of these compounds were determined by spectroscopic methods and chemical syntheses. We also examined the acute toxicities of these substances in mice and their binding to beta-adrenergic receptors using rat cerebellum cortex membranes. Although the photoproducts isolated in this study did not exhibit any acute toxicity or significant binding to beta-adrenergic receptors, these results serve as a warning to single-dose packaging systems, as propranolol (1) must be handled carefully to protect the compound from light-induced degradation.

  14. The orthosteric GABAA receptor ligand Thio-4-PIOL displays distinctly different functional properties at synaptic and extrasynaptic receptors

    DEFF Research Database (Denmark)

    Hoestgaard-Jensen, K; O'Connor, R M; Dalby, Nils Ole

    2013-01-01

    Explorations into the heterogeneous population of native GABA type A receptors (GABAA Rs) and the physiological functions governed by the multiple GABAA R subtypes have for decades been hampered by the lack of subtype-selective ligands....

  15. Indian populations

    CERN Document Server

    Spahni,J

    1974-01-01

    Le Prof. J.C. Spahni qui a parcouru les Andes, Vénezuela etc. parle de ses expériences et connaissances qu'il a vécu au cours des 14 ans parmi les populations indiennes de la Cordillière des Andes. Il a ramené des objets artisanals indiens lesquels l'auditoire peut acquérir. L'introduction-conférence est suivi d'un film, commenté par lui-même; après l'entracte il y un débat-dialogue avec le public.

  16. Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population

    Directory of Open Access Journals (Sweden)

    Budai Barna

    2008-11-01

    Full Text Available Abstract Background Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation. Methods 538 Hungarian subjects were studied: 278 patients with colorectal cancer and 260 healthy controls. Median follow-up was 17 months. After genotyping, the relationship between LCT 13910 C/T and CaSR A986S polymorphisms as well as tumor incidence/progression was investigated. Results in patient with colorectal cancer, a significantly higher LCT CC frequency was associated with increased distant disease recurrence (OR = 4.04; 95% CI = 1.71–9.58; p = 0.006. The disease free survival calculated from distant recurrence was reduced for those with LCT CC genotype (log rank test p = 0.008. In case of CaSR A986S polymorphism, the homozygous SS genotype was more frequent in patients than in controls (OR = 4.01; 95% CI = 1.33–12.07; p = 0.014. The number of LCT C and CaSR S risk alleles were correlated with tumor incidence (p = 0.035. The CCSS genotype combination was found only in patients with CRC (p = 0.033. Conclusion LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC.

  17. Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome

    DEFF Research Database (Denmark)

    Karrman, Kristina; Forestier, Erik; Heyman, Mats

    2009-01-01

    Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87...... incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively....... In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of > or =200 x 10(9)/l (P

  18. Glucocorticoid receptor knockdown and adult hippocampal neurogenesis

    NARCIS (Netherlands)

    Hooijdonk, Leonarda Wilhelmina Antonia van

    2010-01-01

    The research in this thesis is aimed at the elucidation of the role of the glucocorticoid receptor (GR) in hippocampal neuroplasticity and functioning. To achieve this, we have developed a novel method to specifically knockdown GR in a discrete cell population of the mouse brain. In this thesis I r

  19. Association between depression, pressure pain sensitivity, stress and autonomous nervous system function in stable ischemic heart disease

    DEFF Research Database (Denmark)

    Ballegaard, Søren; Bergmann, Natasha; Karpatschof, Benny

    2016-01-01

    table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction....... Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting...... in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors....

  20. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

    Directory of Open Access Journals (Sweden)

    Liang Shu-Fen

    2006-04-01

    Full Text Available Abstract Background Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR. The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP with Bst N1 used for codon 972 and Dra III for codon 513. Results AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%. None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated

  1. The modulation of cell surface cAMP receptors from Dictyostelium disscoideum by ammonium sulfate

    NARCIS (Netherlands)

    Haastert, Peter J.M. van

    1985-01-01

    Dictyostelium discoideum cells contain a heterogeneous population of cell surface cAMP receptors with components possessing different affinities (Kd between 15 and 450 nM) and different off-rates of the cAMP-receptor complex (t½ between 0.7 and 150 s). The association of cAMP to the receptor and the

  2. Population Genetics with Fluctuating Population Sizes

    CERN Document Server

    Chotibut, Thiparat

    2016-01-01

    Standard neutral population genetics theory with a strictly fixed population size has important limitations. An alternative model that allows independently fluctuating population sizes and reproduces the standard neutral evolution is reviewed. We then study a situation such that the competing species are neutral at the equilibrium population size but population size fluctuations nevertheless favor fixation of one species over the other. In this case, a separation of timescales emerges naturally and allows adiabatic elimination of a fast population size variable to deduce the fluctuations-induced selection dynamics near the equilibrium population size. The results highlight the incompleteness of the standard population genetics with a strictly fixed population size.

  3. Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, P.A.; Lowrey, P.

    1987-04-01

    Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC/sub 50/s of 100, 100, and 500 nM, respectively. These actions were blocked by the ..beta..-adrenergic antagonist, propranolol, but not by the ..cap alpha..-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10/sup -6/ M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10/sup -5/ M isotocin and slightly decreased by 10/sup -6/ M angiotensin II. (/sup 125/I)-iodocyanopindolol (ICP), a ..beta..-adrenergic ligand, bound to isolated carp liver membranes with a K/sub D/ of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with K/sub D/s of 100 nM, 2, 20, 20, 60, and 200 ..mu..M, respectively. The ..cap alpha..-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via ..beta..-adrenergic receptors in carp liver and that ..cap alpha..-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.

  4. Spatial Distribution of the Cannabinoid Type 1 and Capsaicin Receptors May Contribute to the Complexity of Their Crosstalk

    OpenAIRE

    2016-01-01

    The cannabinoid type 1 (CB1) receptor and the capsaicin receptor (TRPV1) exhibit co-expression and complex, but largely unknown, functional interactions in a sub-population of primary sensory neurons (PSN). We report that PSN co-expressing CB1 receptor and TRPV1 form two distinct sub-populations based on their pharmacological properties, which could be due to the distribution pattern of the two receptors. Pharmacologically, neurons respond either only to capsaicin (COR neurons) or to both cap...

  5. Acetylcholine receptor antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  6. Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2015-12-01

    Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

  7. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of t

  8. Evolution of endothelin receptors in vertebrates.

    Science.gov (United States)

    Braasch, Ingo; Schartl, Manfred

    2014-12-01

    Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

  9. Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex.

    Science.gov (United States)

    Damian, Marjorie; Mary, Sophie; Maingot, Mathieu; M'Kadmi, Céline; Gagne, Didier; Leyris, Jean-Philippe; Denoyelle, Séverine; Gaibelet, Gérald; Gavara, Laurent; Garcia de Souza Costa, Mauricio; Perahia, David; Trinquet, Eric; Mouillac, Bernard; Galandrin, Ségolène; Galès, Céline; Fehrentz, Jean-Alain; Floquet, Nicolas; Martinez, Jean; Marie, Jacky; Banères, Jean-Louis

    2015-02-03

    How G protein-coupled receptor conformational dynamics control G protein coupling to trigger signaling is a key but still open question. We addressed this question with a model system composed of the purified ghrelin receptor assembled into lipid discs. Combining receptor labeling through genetic incorporation of unnatural amino acids, lanthanide resonance energy transfer, and normal mode analyses, we directly demonstrate the occurrence of two distinct receptor:Gq assemblies with different geometries whose relative populations parallel the activation state of the receptor. The first of these assemblies is a preassembled complex with the receptor in its basal conformation. This complex is specific of Gq and is not observed with Gi. The second one is an active assembly in which the receptor in its active conformation triggers G protein activation. The active complex is present even in the absence of agonist, in a direct relationship with the high constitutive activity of the ghrelin receptor. These data provide direct evidence of a mechanism for ghrelin receptor-mediated Gq signaling in which transition of the receptor from an inactive to an active conformation is accompanied by a rearrangement of a preassembled receptor:G protein complex, ultimately leading to G protein activation and signaling.

  10. [Melatonin receptor agonist].

    Science.gov (United States)

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  11. Dopamine receptors and hypertension.

    Science.gov (United States)

    Banday, Anees Ahmad; Lokhandwala, Mustafa F

    2008-08-01

    Dopamine plays an important role in regulating renal function and blood pressure. Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney. Dopamine acts via cell surface receptors coupled to G proteins; the receptors are classified via pharmacologic and molecular cloning studies into two families, D1-like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5 receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation. Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine production and/or dopamine receptor function in human primary hypertension and in genetic models of animal hypertension. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to hypertension. A primary defect in D1-like receptors and an altered signaling system in proximal tubules may reduce dopamine-mediated effects on renal sodium excretion. The molecular basis for dopamine receptor dysfunction in hypertension is being investigated, and may involve an abnormal posttranslational modification of the dopamine receptor.

  12. CB2 receptors in the brain: role in central immune function

    OpenAIRE

    Cabral, G. A.; Raborn, E S; Griffin, L.; Dennis, J.; Marciano-Cabral, F

    2007-01-01

    Recently, it has been recognized that the cannabinoid receptor CB2 may play a functionally relevant role in the central nervous system (CNS). This role is mediated primarily through microglia, a resident population of cells in the CNS that is morphologically, phenotypically, and functionally related to macrophages. These cells also express the cannabinoid receptor CB1. The CB1 receptor (CB1R) is constitutively expressed at low levels while the CB2 receptor (CB2R) is expressed at higher levels...

  13. Evidence for adaptation of porcine Toll-like receptors

    NARCIS (Netherlands)

    Darfour-Oduro, Kwame A.; Megens, Hendrik Jan; Roca, Alfred; Groenen, Martien A.M.; Schook, Lawrence B.

    2016-01-01

    Naturally endemic infectious diseases provide selective pressures for pig populations. Toll-like receptors (TLRs) represent the first line of immune defense against pathogens and are likely to play a crucial adaptive role for pig populations. This study was done to determine whether wild and dome

  14. Receptor-Like Kinases in Plant Innate Immunity

    Institute of Scientific and Technical Information of China (English)

    Ying Wu; Jian-Min Zhou

    2013-01-01

    Plants employ a highly effective surveillance system to detect potential pathogens, which is critical for the success of land plants in an environment surrounded by numerous microbes. Recent efforts have led to the identification of a number of immune receptors and components of immune receptor complexes. It is now clear that receptor-like kinases (RLKs) and receptor-like proteins (RLPs) are key pattern-recognition receptors (PRRs) for microbe- and plant-derived molecular patterns that are associated with pathogen invasion. RLKs and RLPs involved in immune signaling belong to large gene families in plants and have undergone lineage specific expansion. Molecular evolution and population studies on phytopathogenic molecular signatures and their receptors have provided crucial insight into the co-evolution between plants and pathogens.

  15. Mammalian odorant receptors: functional evolution and variation.

    Science.gov (United States)

    Jiang, Yue; Matsunami, Hiroaki

    2015-10-01

    In mammals, the perception of smell starts with the activation of odorant receptors (ORs) by volatile molecules in the environment. The mammalian OR repertoire has been subject to rapid evolution, and is highly diverse within the human population. Recent advances in the functional expression and ligand identification of ORs allow for functional analysis of OR evolution, and reveal that changes in OR protein sequences translate into high degrees of functional variations. Moreover, in several cases the functional variation of a single OR affects the perception of its cognate odor ligand, providing clues as to how an odor is coded at the receptor level.

  16. 中国人群FGFR2基因多态性与乳腺癌易感相关性研究的Meta分析%Fibroblast growth factor receptor 2 polymorphism and susceptibility to breast cancer in Chinese population:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    邱秀娟; 成芳; 高俊

    2015-01-01

    OBJECTIVE To evaluate the association between the fibroblast growth factor receptor 2 (FGFR2) gene polymorphism (rs2981582,rs1219648,rs2420946) and the breast cancer risk in the Chinese populations.METHODS All studies published up to June 2014 on the association between three functional polymorphisms (rs2981582,rs1219648,rs2420946) in the promoter of FGFR2 gene and susceptibility to breast cancer in Chinese population were collected by searching PubMed,Embase,Cochrane library,CNKI,VIP,Wanfang and CBD database.The data were screened according to the inclusion and exclusion criteria,and extracted,and the quality of included studies was evaluated.The pooled odds ratios (OR) with 95 % confidence intervals (95 % CI) were calculated using Stata 12.0 software.Publication bias and sensitivity analysis were also assessed.RESULTS A total of 18 case-control studies involving 14568 cases and 12864 controls were included in the Meta-analysis.The FGFR2 rs2981582,rs1219648,rs2420946 polymorphisms were significantly associated with breast cancer risk susceptibility among Chinese populations.The subgroup analysis by region revealed that significant risks were found in southern and northern China populations for rs2981582 T allele(southern:OR=1.13,95 %CI:1.06-1.22,P =0.001 ; northern:OR =1.26,95% CI..1.06-1.49,P =0.008).Significant risks were found in southern China populations for rs2420946 T allele (OR=1.15,95 % CI:1.08-1.23,P<0.05),but not in northern China populations (OR=1.03,95 % CI:0.87-1.22,P =0.695).Significant risks were found in southern and northern China populations for rs1219648 G allele(southern:OR=1.19,95%CI:1.10-1.28,P<0.05; northern:OR=1.17,95%CI:1.00-1.37,P=0.05).CONCLUSION The FGFR2 rs2981582,rs1219648,rs2420946 polymorphisms are significantly associated with breast cancer risk susceptibility among Chinese populations.%目的 系统评估成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)基因内含子的3

  17. Distribution of Angiotensin Ⅱ Type 1 Receptor Gene A1166C Polymorphism in Yi Nationality Population in Yunnan Province%血管紧张素Ⅱ1型受体A1166C多态性在云南彝族人群中的分布

    Institute of Scientific and Technical Information of China (English)

    杨榆玲; 龙莉; 瞿秋; 吴玲; 何永蜀; 张彦

    2012-01-01

    目的 了解云南省晋宁县彝族人群AT1R基因A1166C多态性分布的情况,为研究AT1R基因相关性疾病的发病机制奠定基础.方法 采用PCR-RFLP技术对居住在云南省晋宁县180例彝族健康个体的AT1R基因A1166C多态性进行分析,获得其基因型频率和等位基因频率分布情况,并与其他人群该位点多态性进行比较.结果 云南省晋宁县彝族AT1R基因的AA、AC、CC基因型频率分别为95.6%、4.4%和0%,A、C等位基因频率分别为97.8%和2.2%.此位点多态性分布与不同人群比较,除凉山彝族外,差异均有统计学意义(P<0.05).结论 AT1R基因A1166C多态性分布存在民族、种族差异.%Objective To investigate the angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in a Yi nationality population in Yunnan province, and to provide evidence for the research of AT1R related diseases. Methods We recruited 180 healthy subjects of Yi nationality in rural area of Jinning, Yunnan province. The AT1R A1166C polymorphism was determined by polymerase chain reaction- restriction fragment (PCR- RFLP) technique. The genotype frequencies and allele frequencies were obtained and compared with those collected from other population. Results In healthy Yi people of Yunnan province, frequencies for the AA, AC and CC genotypes were 95.6%, 4.4% and 0%. Derived allele frequencies for the A and C allele were 97.8% and 2.2%. The distribution of AT1R genotypes and the allele frequencies in Yunnan Yi people were significantly different from other nationality (P<0.05) . Conclusion The frequency of the genotype or the allele of AT1R A1166C polymorphism is different significantly in different ethnic populations.

  18. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  19. Thyroid hormones and renin secretion.

    Science.gov (United States)

    Ganong, W F

    Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons, in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by beta-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased beta-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased beta-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

  20. The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle.

    Science.gov (United States)

    Chinsomboon, Jessica; Ruas, Jorge; Gupta, Rana K; Thom, Robyn; Shoag, Jonathan; Rowe, Glenn C; Sawada, Naoki; Raghuram, Srilatha; Arany, Zoltan

    2009-12-15

    Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPARgamma coactivator (PGC)-1alpha is a potent transcriptional co-activator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1alpha mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1alpha in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1alpha from an alternate promoter. The induction of PGC-1alpha depended on beta-adrenergic signaling. beta-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1alpha. The orphan nuclear receptor ERRalpha mediated the induction of VEGF by PGC-1alpha, and mice lacking ERRalpha also failed to increase vascular density after exercise. These data demonstrate that beta-adrenergic stimulation of a PGC-1alpha/ERRalpha/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle.

  1. Effective population size of korean populations.

    Science.gov (United States)

    Park, Leeyoung

    2014-12-01

    Recently, new methods have been developed for estimating the current and recent changes in effective population sizes. Based on the methods, the effective population sizes of Korean populations were estimated using data from the Korean Association Resource (KARE) project. The overall changes in the population sizes of the total populations were similar to CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) of the HapMap project. There were no differences in past changes in population sizes with a comparison between an urban area and a rural area. Age-dependent current and recent effective population sizes represent the modern history of Korean populations, including the effects of World War II, the Korean War, and urbanization. The oldest age group showed that the population growth of Koreans had already been substantial at least since the end of the 19th century.

  2. Novel cannabinoid receptors

    OpenAIRE

    Brown, A J

    2007-01-01

    Cannabinoids have numerous physiological effects. In the years since the molecular identification of the G protein-coupled receptors CB1 and CB2, the ion channel TRPV1, and their corresponding endogenous ligand systems, many cannabinoid-evoked actions have been shown conclusively to be mediated by one of these specific receptor targets. However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology. Studies using mice genetically delete...

  3. 干扰素调节因子5、维生素D受体、β防御素1和Toll样受体4的基因多态性与汉族人群克罗恩病的相关性%gene polymorphism and Crohn′s disease in Han population Correlation between interferon regulatory factor 5 ,vitamin D receptor ,beta-defensin 1 ,Toll-like receptor 4

    Institute of Scientific and Technical Information of China (English)

    李攀; 沈冰冰; 吕红; 杨红; 杨晓鸥; 钱家鸣

    2015-01-01

    目的 探讨干扰素调节因子5(IRF5)、维生素D受体(VDR)、β防御素1和 TLR4的基因多态性与汉族人群CD易感性的关系.方法 收集2007年1月至2011年5月就诊的158例CD患者与246名健康体格检查者的资料与血清标本.采用高通量质谱分析方法对 IRF5、VDR、β防御素1和TLR4这4个基因的14个标签单核苷酸多态性(SNP)的基因型进行检测.CD组与健康对照组率的比较采用卡方检验.应用多因子降维法(MDR)对上述候选基因之间的联合作用与CD易感性的关系进行分析.结果 基于等位基因或基因型的关联分析均未发现 IRF5、VDR、β防御素1和 TLR4这4个候选基因与CD易感性相关(P均> 0 .05).基于单体型的关联分析显示 ,IRF5基因单体型区域中的GTACC单体型在CD组与健康对照组中出现的频率分别为0 .046和0 .089 ,差异有统计学意义(χ2 =5 .223 ,P=0 .022 3).基因型与临床表型的分析结果显示 ,CD患者β防御素1基因rs2978880的基因型分别为C/C ,C/T , T/T ,有手术史的分布频率分别为0 .235、0 .603、0 .162 ,无手术史的分别为0 .482、0 .388、0 .129 ,其中C/C等位基因型患者的肠道手术风险相对较低(χ2 =10 .065 ,P=0 .006).MDR分析未发现上述基因位点与CD易感性之间存在交互作用(P均>0 .05).结论 IRF5的GTACC单体型与汉族CD人群的易感性相关 ,β防御素1基因rs2978880位点C/C纯合基因型与汉族CD人群的临床表型相关.%Objective To investigate the correlation between interferon regulatory factor 5 (IRF5) ,vitamin D receptor (VDR ) ,beta-defensin 1 (DEFB1 ) ,Toll-like receptor 4 (TLR4 ) gene polymorphismand Crohn′s disease (CD) in Chinese Han population .Methods From January 2007 to May 2011 ,thedata and serum samples of 158 CD patients and 246 healthy controls were collected .The genotype of 14tag single-nucleotide polymorphisms (SNP) of IRF5 ,VDR ,DEFB1 and TLR4 were detected .Chi-squaretest was performed for rate

  4. Prenatal exposure to methylmercury alters development of adrenergic receptor binding sites in peripheral sympathetic target tissues

    Energy Technology Data Exchange (ETDEWEB)

    Slotkin, T.A.; Orband, L.; Cowdery, T.; Kavlock, R.J.; Bartolome, J.

    1987-01-01

    In order to assess the impact of prenatal exposure to methylmercury on sympathetic neurotransmission, effects on development of adrenergic receptor binding sites in peripheral tissues was evaluated. In the liver, methylmercury produced a dose-dependent increase in alpha/sub 1/, alpha/sub 2/, and beta-receptor binding of radioliganda throughout the first 5 weeks of postnatal life. Similarly, renal alpha-receptor subtypes showed increased binding capabilities, but binding to alpha-receptor sites was reduced. At least some of the changes in receptors appear to be of functional significance, as physiological reactivity to adrenergic stimulation is altered in the same directions in these two tissues. The actions of methylmercury displayed tissue specificity in that the same receptor populations were largely unaffected in other tissues (lung, heart). These results suggest that methylmercury exposure in utero alters adrenergic responses through targeted effects on postsynaptic receptor populations in specific tissues.

  5. Low nanomolar GABA effects at extrasynaptic a4ß1/ß3delta GABAA receptor subtypes indicate a different binding mode for GABA at these receptors

    DEFF Research Database (Denmark)

    Karim, Nasiara; Wellendorph, Petrine; Absalom, Nathan;

    2012-01-01

    Ionotropic GABA(A) receptors are a highly heterogenous population of receptors assembled from a combination of multiple subunits. The aims of this study were to characterize the potency of GABA at human recombinant d-containing extrasynaptic GABA(A) receptors expressed in Xenopus oocytes using th...

  6. Progesterone Receptor Scaffolding Function in Breast Cancer

    Science.gov (United States)

    2012-10-01

    the population of mammary stem cells (via paracrine signaling) [22; 23] and for coordinating the dynamic (proliferative) regulation of glandular ...contrast to PR/ER expres- sion in just 7 to 10% of normal breast luminal epithelium (67). As steroid hormone receptor (SR)-positive tumors progress...mammary epithelium during puberty and pregnancy (in preparation for lactation), but may inappropriately drive early breast cancer progression of

  7. [The LDL receptor family].

    Science.gov (United States)

    Meilinger, Melinda

    2002-12-29

    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  8. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f...

  9. Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit counting

    Science.gov (United States)

    Durisic, Nela; Godin, Antoine G.; Wever, Claudia M.; Heyes, Colin D.; Lakadamyali, Melike; Dent, Joseph A.

    2012-01-01

    The subunit stoichiometry of heteromeric glycine-gated channels (GlyRs) determines fundamental properties of these key inhibitory neurotransmitter receptors; however the ratio of α1 to β-subunits per receptor remains controversial. We used single molecule imaging and stepwise photobleaching in Xenopus oocytes to directly determine the subunit stoichiometry of a glycine receptor to be 3α1:2β. This approach allowed us to determine the receptor stoichiometry in mixed populations consisting of both heteromeric and homomeric channels, additionally revealing the quantitative proportions for the two populations. PMID:22973015

  10. Drug: D00644 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00644 Drug Esmolol hydrochloride (JAN/USAN); Brevibloc (TN) C16H25NO4. HCl 331.155... 331.8349 D00644.gif Anti-adrenergic [beta-receptor] Therapeutic category: 2123 ATC code: C07AB09 beta1-adre...active ligand-receptor interaction hsa04261(153) Adrenergic signaling in cardiomy...ocytes hsa04970(153) Salivary secretion map07214 beta-Adrenergic receptor agonists/antagonists Therapeutic category of dr...iarrhythmic agents 2123 Beta blockers D00644 Esmolol hydrochloride (JAN/USAN) Ana

  11. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  12. Characterization and pharmacology of the GHB receptor.

    Science.gov (United States)

    Ticku, Maharaj K; Mehta, Ashok K

    2008-10-01

    Radioligand binding using [(3)H]NCS-382, an antagonist of the GHB receptor, revealed specific binding sites in the rat cerebrocortical and hippocampal membranes. Scatchard analysis of saturation isotherms revealed two different populations of binding sites. NCS-382 was about 10 times more potent than GHB in inhibiting [(3)H]NCS-382 binding. A variety of ligands for other receptors did not affect [(3)H]NCS-382 binding. Quantitative autoradiographic analysis of [(3)H]NCS-382 binding revealed similar characteristics. Thus [(3)H]NCS-382, being more potent and selective, offers advantage over [(3)H]GHB as a radioligand. Unlike GHB, several analogues of GHB such as UMB68 (a tertiary alcohol analogue of GHB), UMB86 (4-hydroxy-4-napthylbutanoic acid, sodium salt), UMB72 [4-(3-phenylpropyloxy)butyric acid, sodium salt], UMB73 (4-benzyloxybutyric acid, sodium salt), UMB66 (3-chloropropanoic acid), gamma-hydroxyvaleric acid (that is, GHV, a 4-methyl-substituted analogue of GHB), 3-HPA (3-hydroxyphenylacetic acid), and ethers of 3-hydroxyphenylacetic acid (UMB108, UMB109, and UMB119) displaced [(3)H]NCS-382 without affecting [(3)H]GABA binding to GABA(B) receptor. Thus these compounds offer an advantage over GHB as an experimental tool. Our study, aimed at exploring the potential involvement of the GHB receptor in the pharmacology of ethanol, indicated that ethanol does not affect [(3)H]NCS-382 binding in the rat brain, thereby suggesting that ethanol does not interact directly with the GHB receptor. Our study, aimed at exploring the involvement of the GHB receptor in the pathology of succinate semialdehyde dehydrogenase deficiency, which is known to cause elevation of GHB levels, revealed no change in the affinity, receptor density or displacement potency as determined by using [(3)H]NCS-382 as a radioligand in Aldh5a1(-/-) vs. Aldh5a1(+/+) mouse brain.

  13. Education Vital Signs: Population.

    Science.gov (United States)

    Zakariya, Sally Banks

    1985-01-01

    Population changes and demographics shape the future of public schools. Includes statistics on ethnic makeup of student population, the projected baby boomlet, children of working mothers, households without children, and the aging population. (MD)

  14. Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction.

    Science.gov (United States)

    Borodinsky, Laura N; Spitzer, Nicholas C

    2007-01-02

    Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their receptors in the assembly of functional synapses.

  15. Opiate receptors: an introduction.

    Science.gov (United States)

    Carmody, J J

    1987-02-01

    Current status of opiate receptors and their agonists is reviewed--basic aspects of receptor theory, the importance of stereospecificity in drug-receptor interactions and the role of 'second messengers' in drug action. The three classes of endogenous opioids, originating from three distinct genes, are discussed: pro-opiomelanocortin, giving rise to beta-endorphin, ACTH and various MSHs; pro-enkephalin, giving methionine enkephalin and leucine enkephalin; and prodynorphin; their anatomical distribution and the main classes of receptors with which they interact, the mu-receptor, with a high affinity for met-enkephalin and beta-endorphin (as well as morphine and dynorphin A); the delta-receptor for which the primary ligand is leu-enkephalin; and the kappa-receptor which is the main target for the dynorphins. Functional roles for endogenous opioids are considered. Essentially they are inhibitory to target neurones, depressing motor reflexes, baroreflexes and nociception. They also have roles in the response to physical and psychological stress.

  16. Dopamine receptor and hypertension.

    Science.gov (United States)

    Zeng, Chunyu; Eisner, Gilbert M; Felder, Robin A; Jose, Pedro A

    2005-01-01

    Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and reactive oxygen and by interacting with vasopressin, renin-angiotensin, and the sympathetic nervous system. Decreased renal dopamine production and/or impaired dopamine receptor function have been reported in hypertension. Disruption of any of the dopamine receptors (D(1), D(2), D(3), D(4), and D(5)) results in hypertension. In this paper, we review the mechanisms by which hypertension develops when dopamine receptor function is perturbed.

  17. Serotonin Receptors in Hippocampus

    Directory of Open Access Journals (Sweden)

    Laura Cristina Berumen

    2012-01-01

    Full Text Available Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  18. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  19. Serotonin receptors in hippocampus.

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  20. Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats.

    OpenAIRE

    Pellegrini-Giampietro, D E; Zukin, R.S.; Bennett, M V; Cho, S; Pulsinelli, W. A.

    1992-01-01

    Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeab...

  1. Human Population Problems

    Science.gov (United States)

    Emmel, Thomas C.; Sligh, Michael M.

    1970-01-01

    Asserts that overpopulation is the most pressing world problem. Topics discussed include population control in primitive societies, population growth and control in modern societies, methods of motivational population control, consequences of no population control, and mass famines during the 1970's in underdeveloped countries. Cities 33…

  2. Understanding Rural Population Loss.

    Science.gov (United States)

    McGranahan, David A.; Beale, Calvin L.

    2002-01-01

    A quarter of nonmetro counties lost population in the 1990s, but population loss was not related to poverty rate or low educational levels, perhaps because low-skill workers can no longer expect better wages in urban areas. Population loss was related to low population density and remoteness (which decrease access to services), lack of natural…

  3. Why Population in 1974?

    Science.gov (United States)

    O'Connor, Marion

    1974-01-01

    Discusses the impact of world population growth leading to the establishment of the United Nations Fund for Population Activities and to the declaration of 1974 as World Population Year. Previews some of the parameters and interconnecting interests to be considered during this year of intensive population study. (JR)

  4. Acute and chronic cardiovascular effects of hyperkalemia: new insights into prevention and clinical management.

    Science.gov (United States)

    McCullough, Peter A; Beaver, Thomas M; Bennett-Guerrero, Elliott; Emmett, Michael; Fonarow, Gregg C; Goyal, Abhinav; Herzog, Charles A; Kosiborod, Mikhail; Palmer, Biff F

    2014-01-01

    The plasma pool of potassium is a partial reflection of the overall body, transient cellular shifts, and potassium elimination regulated by the kidneys. Potassium concentrations elevating above the upper limit of normal (> 5.0 mEq/L) have become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad applications of drugs that modulate potassium excretion by either reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, beta-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). In addition, acute kidney injury, critical illness, crush injuries, and massive red blood cell transfusions can result in hyperkalemia. Progressively more severe elevations in potassium are responsible for abnormalities in cardiac depolarization and repolarization and contractility. Untreated severe hyperkalemia results in sudden cardiac death. Traditional management steps have included reducing dietary potassium and discontinuing potassium supplements; withdrawal of exacerbating drugs; acute treatment with intravenous calcium gluconate, insulin, and glucose; nebulized albuterol; correction of acidosis with sodium bicarbonate for short-term shifts out of the plasma pool; and, finally, gastrointestinal ion exchange with oral sodium polystyrene sulfonate in sorbitol, which is mainly used in the hospital and is poorly tolerated due to gastrointestinal adverse effects. This review explores hyperkalemia as a complication in cardiovascular patients and highlights new acute, chronic, and preventative oral therapies (patiromer calcium, cross-linked polyelectrolyte, ZS-9) that could potentially create a greater margin of safety for vulnerable patients with combined heart and kidney disease.

  5. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael

    2005-01-01

    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects...

  6. Update on Melatonin Receptors. IUPHAR Review. : Melatonin Receptors

    OpenAIRE

    Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita ,; Markus, Regina ,; Renault, Nicolas; Tosini, Gianluca; Cecon, Erika; Zlotos, Darius Paul

    2016-01-01

    International audience; Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including ...

  7. Histamine receptors in isolated bovine oviductal arteries.

    Science.gov (United States)

    Martínez, A C; Novella, S; Raposo, R; Recio, P; Labadía, A; Costa, G; Garcia-Sacristán, A; Benedito, S

    1997-05-20

    The present in vitro study was designed to evaluate the effect of histamine on isolated rings of bovine oviductal artery and to characterize the histamine receptors involved in the histamine-induced response. Endothelial dependence of the response was also investigated. Cumulative addition of histamine and 2-pyridylethylamine (histamine H receptor agonist) induced a concentration-dependent relaxation in intact arterial segments precontracted with noradrenaline. The histamine H1 receptor antagonist mepyramine showed non-competitive antagonism in the histamine-induced concentration-response curve. However, when the response to histamine was evaluated in the presence of mepyramine and histamine H1 and H3 receptors were blocked, Schild analysis yielded a line with a slope of 1.10 and a pA2 value of 8.91, indicating simple competitive antagonism of mepyramine at histamine H1 receptor sites. The histamine H2 receptor agonist, dimaprit, caused marked dilatation only at high doses. Cimetidine, propranolol and mepyramine failed to inhibit this relaxant effect. In precontracted oviductal arteries, cimetidine did not modify the histamine-induced concentration-response curves. Combined treatment with histamine H1 and H2 receptor antagonists did not induce an additional displacement with respect to the isolated effect of mepyramine thus excluding activation of histamine H2 receptors. Histamine and (R)-alpha-methylhistamine, a selective histamine H3 receptor agonist, produced a moderate contractile effect on the resting tone of preparations. Pretreatment with the selective histamine H1 receptor antagonist decreased the (R)-alpha-methylhistamine response but increased the maximal relaxant effect and abolished the contractile effect of histamine, suggesting the presence of a limited population of contractile histamine H3 receptors. Removal of the endothelium or pretreatment with methylene blue produced a significant inhibition of the relaxant response to histamine. Remaining

  8. Receptors for enterovirus 71

    OpenAIRE

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2014-01-01

    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays crit...

  9. Serotonin Receptors in Hippocampus

    OpenAIRE

    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a fu...

  10. Population Dynamics of Viral Inactivation

    Science.gov (United States)

    Freeman, Krista; Li, Dong; Behrens, Manja; Streletzky, Kiril; Olsson, Ulf; Evilevitch, Alex

    We have investigated the population dynamics of viral inactivation in vitrousing time-resolved cryo electron microscopy combined with light and X-ray scattering techniques. Using bacteriophage λ as a model system for pressurized double-stranded DNA viruses, we found that virions incubated with their cell receptor eject their genome in a stochastic triggering process. The triggering of DNA ejection occurs in a non synchronized manner after the receptor addition, resulting in an exponential decay of the number of genome-filled viruses with time. We have explored the characteristic time constant of this triggering process at different temperatures, salt conditions, and packaged genome lengths. Furthermore, using the temperature dependence we determined an activation energy for DNA ejections. The dependences of the time constant and activation energy on internal DNA pressure, affected by salt conditions and encapsidated genome length, suggest that the triggering process is directly dependent on the conformational state of the encapsidated DNA. The results of this work provide insight into how the in vivo kinetics of the spread of viral infection are influenced by intra- and extra cellular environmental conditions. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1252522.

  11. Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

    Science.gov (United States)

    Matute, Carlos; Sánchez-Gómez, M. Victoria; Martínez-Millán, Luis; Miledi, Ricardo

    1997-01-01

    In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription–PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-d-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population. PMID:9238063

  12. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases.

  13. [BETA-ADRENERGIC REGULATION OF THE ADENYLYL CYCLASE SIGNALING SYSTEM IN MYOCARDIUM AND BRAIN OF RATS WITH OBESITY AND TYPES 2 DIABETES MELLITUS AND THE EFFECT OF LONG-TERM INTRANASAL INSULIN TREATMENT].

    Science.gov (United States)

    Kuznetsova, L A; Sharova, T S; Pertseva, M N; Shpakov, A O

    2015-01-01

    The stimulating effect of norepinephrine, isoproterenol and selective β-adrenoceptor (β3-AR) agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats (disease induction at 2 and 4 months, respectively) with experimental obesity and type 2 diabetes mellitus (DM2), and the influence of long-term treatment of animals with intranasal insulin (I-I) were studied. The AC stimulatory effects of β-agonist isoproterenol in animals with obesity and DM2 was shown to be practically unchanged. The respective effects of norepinephrine on the AC activity were attenuated in the brain of young and mature rats and in the myocardium if mature rats, and the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2, the enhancement of the AC stimulatory effects of β3-AR agonists was observed, white in young rats the influence of the same pathological conditions was lacking. The I-I treatment decreased the AC stimulatory effects of β3-agonists to their levels in the control. Since functional disruption of the adrenergic agonist-sensitive ACSS can lead to metabolic syndrome and DM2, the recovery of this system by the I-I treatment offers one of the ways to correct these diseases and their complications in the nervous and cardiovascular systems.

  14. Nature's knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters.

    Science.gov (United States)

    Weaver, D R; Liu, C; Reppert, S M

    1996-11-01

    The pineal hormone melatonin regulates seasonal reproduction and influences the timing of circadian rhythms. The Mel1a and Mel1b receptors are the high-affinity melatonin receptors present in mammals. Unexpectedly, the Mel1b receptor gene of the Siberian hamster, Phodopus sungorus, cannot encode a functional receptor; two nonsense mutations are present within the coding region. Southern blot analysis indicates that this is a single copy gene. The Mel1b receptor gene is nonfunctional in outbred populations of P. sungorus and Phodopus campbelli. Siberian hamsters lacking a functional Mel1b receptor nevertheless show seasonal reproductive and circadian responses to melatonin, indicating that the Mel1b receptor is not necessary for these responses. These data support the hypothesis that the Mel1a receptor, which does encode a functional receptor in this species, mediates reproductive and circadian responses to melatonin.

  15. Drug: D00600 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00600 Drug Labetalol hydrochloride (JP16/USP); Normodyne (TN); Trandate (TN) C19H2...nts 214 Antihypertensives 2149 Others D00600 Labetalol hydrochloride (JP16/USP) Anatomical Therapeutic Chemi...ENTS C07AG Alpha and beta blocking agents C07AG01 Labetalol D00600 Labetalol hydrochloride (JP16/USP) USP dr...ug classification [BR:br08302] Cardiovascular Agents Beta-adrenergic Blocking Agents Labetalol D00600 Lab...Protein-coupled receptors Rhodopsin family Adrenaline alpha1-adrenergic receptor [HSA:146 147 148] [KO:K04137 K04136 K04135] Lab

  16. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  17. Increased YKL-40 expression in patients with carotid atherosclerosis

    DEFF Research Database (Denmark)

    Michelsen, Annika E; Rathcke, Camilla N; Skjelland, Mona

    2010-01-01

    atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. RESULTS: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

  18. Increased YKL-40 expression in patients with carotid atherosclerosis

    DEFF Research Database (Denmark)

    Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.

    2010-01-01

    atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

  19. Sucrose ingestion induces rapid AMPA receptor trafficking.

    Science.gov (United States)

    Tukey, David S; Ferreira, Jainne M; Antoine, Shannon O; D'amour, James A; Ninan, Ipe; Cabeza de Vaca, Soledad; Incontro, Salvatore; Wincott, Charlotte; Horwitz, Julian K; Hartner, Diana T; Guarini, Carlo B; Khatri, Latika; Goffer, Yossef; Xu, Duo; Titcombe, Roseann F; Khatri, Megna; Marzan, Dave S; Mahajan, Shahana S; Wang, Jing; Froemke, Robert C; Carr, Kenneth D; Aoki, Chiye; Ziff, Edward B

    2013-04-03

    The mechanisms by which natural rewards such as sugar affect synaptic transmission and behavior are largely unexplored. Here, we investigate regulation of nucleus accumbens synapses by sucrose intake. Previous studies have shown that AMPA receptor (AMPAR) trafficking is a major mechanism for regulating synaptic strength, and that in vitro, trafficking of AMPARs containing the GluA1 subunit takes place by a two-step mechanism involving extrasynaptic and then synaptic receptor transport. We report that in rat, repeated daily ingestion of a 25% sucrose solution transiently elevated spontaneous locomotion and potentiated accumbens core synapses through incorporation of Ca(2+)-permeable AMPA receptors (CPARs), which are GluA1-containing, GluA2-lacking AMPARs. Electrophysiological, biochemical, and quantitative electron microscopy studies revealed that sucrose training (7 d) induced a stable (>24 h) intraspinous GluA1 population, and that in these rats a single sucrose stimulus rapidly (5 min) but transiently (<24 h) elevated GluA1 at extrasynaptic sites. CPARs and dopamine D1 receptors were required in vivo for elevated locomotion after sucrose ingestion. Significantly, a 7 d protocol of daily ingestion of a 3% solution of saccharin, a noncaloric sweetener, induced synaptic GluA1 similarly to 25% sucrose ingestion. These findings identify multistep GluA1 trafficking, previously described in vitro, as a mechanism for acute regulation of synaptic transmission in vivo by a natural orosensory reward. Trafficking is stimulated by a chemosensory pathway that is not dependent on the caloric value of sucrose.

  20. Unraveling the genetic expression of the highly variable immune receptors of a killer

    NARCIS (Netherlands)

    Vendelbosch, S.

    2015-01-01

    The Killer Immunoglobulin-like Receptors (KIRs) are a family of highly variable receptors which regulate cytotoxicity of Natural Killer (NK) cells and a subset of T-cells. The KIR genes, clustered on the genome in the KIR locus, are distributed unequally across the population due to variation in gen

  1. Epidermal growth factor receptor-targeted antibody therapy - Mechanisms of action and modulators of therapeutic efficacy

    NARCIS (Netherlands)

    Lammerts van Bueren, Jeroen Jilles

    2008-01-01

    Cancer is an increasing disease in the world population, and in recent years there has been substantial interest in the development of novel therapeutic agents specifically targeting growth factor receptors on tumor cells. The epidermal growth factor receptor (EGFR) represents a tyrosine kinase cell

  2. Asseciation of TNF-α gene polymorphisms with Graves disease susceptibility and early course thyroid stimulating hormone receptor antibody level in Chinese Han population in Anhui region%肿瘤坏死因子-α基因多态性与安徽地区汉族人群Graves病易感性及患病早期TRAb水平的关联

    Institute of Scientific and Technical Information of China (English)

    潘天荣; 邢时妹

    2012-01-01

    disease (GD) susceptibility in Chinese Han population in Anhui region.[Methods] The polymorphisms of TNF-α gene were determined by polymerase chain reaction with specific primers in 254 patients affected with GD and 212 healthy controls.Allelic and genotypic frequencies in GD group and normal controls as well as in different genders were compared.The allelic and genotypic frequencies for different thyroid stimulating hormone receptor antibody (TRAb) levels (TRAb > 12 U/L;≤12 U/L) were also compared among patients with earlier onset GD.[Results] (1) The A allele at —863C/A locus in GD group (16.73 %) was significantly greater than that of the control group (11.79%) (P<0.05,OR=1.503);the frequency of AA + CA genotype of —863C/A locus in GD group (32.68%) was significantly greater than that of control group (23.58%) (P<0.05,OR =1.573).There was no significant difference (P>0.05) in the allelic and genotypic frequencies of —857C/ T,—238G/A loci between the two groups.(2) There was no significant difference (P>0.05) in the allelic and genotypic frequencies of —863C/A,—857C/T,—238G/A loci between patients of different genders.(3) There was no significant difference (P>0.05) in such frequencies between patients with earlier onset GD and different TRAb levels (TRAb >12 U/L;≤12 U/L).[Conclusion] (1) The —863 A allele of TNF-α gene may contribute to the development of GD in Chinese Han population in Anhui,whilst —857C/T,—238G/A alleles may not.(2) There is no association between TNF-α gene —863C/A,—857C/T,—238G/A polymorphismns and development of GD in different genders.(3) There was no association between above polymorphisms and TRAb levels in patients with earlier onset GD.

  3. Detection of multiple H3 receptor affinity states utilizing [3H]A-349821, a novel, selective, non-imidazole histamine H3 receptor inverse agonist radioligand.

    Science.gov (United States)

    Witte, David G; Yao, Betty Bei; Miller, Thomas R; Carr, Tracy L; Cassar, Steven; Sharma, Rahul; Faghih, Ramin; Surber, Bruce W; Esbenshade, Timothy A; Hancock, Arthur A; Krueger, Kathleen M

    2006-07-01

    1. A-349821 is a selective histamine H3 receptor antagonist/inverse agonist. Herein, binding of the novel non-imidazole H3 receptor radioligand [3H]A-349821 to membranes expressing native or recombinant H3 receptors from rat or human sources was characterized and compared with the binding of the agonist [3H]N--methylhistamine ([3H]NMH). 2. [3H]A-349821 bound with high affinity and specificity to an apparent single class of saturable sites and recognized human H3 receptors with 10-fold higher affinity compared to rat H3 receptors. [3H]A-349821 detected larger populations of receptors compared to [3H]NMH. 3. Displacement of [3H]A-349821 binding by H3 receptor antagonists/inverse agonists was monophasic, suggesting recognition of a single binding site, while that of H3 receptor agonists was biphasic, suggesting recognition of both high- and low-affinity H3 receptor sites. 4. pKi values of high-affinity binding sites for H3 receptor competitors utilizing [3H]A-349821 were highly correlated with pKi values obtained with [3H]NalphaMH, consistent with labelling of H3 receptors by [3H]A-349821. 5. Unlike assays utilizing [3H]NMH, addition of GDP had no effect on saturation parameters measured with [3H]A-349821, while displacement of [3H]A-349821 binding by the H3 receptor agonist histamine was sensitive to GDP. 6. In conclusion, [3H]A-349821 labels interconvertible high- and low-affinity states of the H3 receptor, and displays improved selectivity over imidazole-containing H3 receptor antagonist radioligands. [3H]A-349821 competition studies showed significant differences in the proportions and potencies of high- and low-affinity sites across species, providing new information about the fundamental pharmacological nature of H3 receptors.

  4. Genetic variants of MARCO are associated with susceptibility to pulmonary tuberculosis in a Gambian population

    OpenAIRE

    Lack, Nathan A.; Bowdish, Dawn M. E.; Sakamoto, Kaori; Hill, Philip C.; Sirugo, Giorgio; Newport, Melanie J.; Gordon, Siamon; Hill, Adrian V. S.; Vannberg, Fredrick O.

    2013-01-01

    Background The two major class A scavenger receptors are scavenger receptor A (SRA), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (MARCO), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. Although the primary role of SRA appears to be clearance of modified host proteins and lipids,...

  5. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  6. The Growing Human Population.

    Science.gov (United States)

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  7. Glaucoma in Asian Populations

    Science.gov (United States)

    ... Us Donate In This Section Glaucoma In Asian Populations email Send this article to a friend by ... an even more serious problem as the world population and longevity increases. The other major glaucoma type ...

  8. Multiple Population Theory: Extreme helium population problem

    OpenAIRE

    Yi, Sukyoung K.

    2009-01-01

    The spreads in chemical abundances inferred by recent precision observations suggest that some or possibly all globular clusters can no longer be considered as simple stellar populations. The most striking case is omega Cen in the sense that its bluest main-sequence despite its high metallicity demands an extreme helium abundance of Y > 0.4. I focus on this issue of "the extreme helium population problem" in this review.

  9. Presynaptic P2 receptors?

    Science.gov (United States)

    Stone, T W; O'Kane, E M; Nikbakht, M R; Ross, F M

    2000-07-01

    Although the emphasis in ATP research has been on postjunctional receptors, there is also evidence for presynaptic receptors regulating transmitter release in the autonomic nervous system. Recent work has attempted to identify similar mechanisms in the central nervous system. Some of the existing results can be explained by the metabolism of nucleotides to adenosine or adenosine 5'-monophosphate (AMP). However, studies of presynaptic effects using sensitive electrophysiological tests such as paired-pulse interactions indicate that nucleotides can act at presynaptic sites, but that their effects may be mediated by a release of adenosine. Results are also described which indicate that, under some conditions, nucleotides can mediate phenomena such as long-term potentiation, which probably involves a significant presynaptic element. In part these effects may involve a nucleotide-induced release of adenosine and the simultaneous activation of P1 and P2 receptors.

  10. Population control charts for population data.

    Science.gov (United States)

    Hansen, John P

    2007-01-01

    Healthcare managers are beginning to collect full population data, rather than sample data, on some patient and performance measures. For example, hospitals and healthcare systems already gather and store comprehensive data on admissions, ambulatory encounters, and other procedures. And as the electronic medical record is more widely used, complete population data will be collected on an even wider range of clinical measures, such as blood pressure and Laboratory values, in both inpatient and outpatient settings. To correctly monitor process quality when working with full population data, rather than sample data, healthcare managers will need appropriate statistical tools. Traditional control charts, which are used for tracking processes over time, are not suitable for such population data because they are based on the assumption that sample data are being collected. The author proposes a new type of control chart specifically for use with such population data: population control charts. These control charts can be used for monitoring processes that have output measures with continuous, binomial, or nonbinomial rate variables.

  11. Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

    Science.gov (United States)

    Kandasamy, S. B.; Williaes, B. A.

    1983-01-01

    It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

  12. Tuning Properties and Dynamic Range of Type 1 Vomeronasal Receptors

    Directory of Open Access Journals (Sweden)

    Sachiko eHaga-Yamanaka

    2015-07-01

    Full Text Available The mouse vomeronasal organ expresses chemosensory receptors that detect intra-species as well as inter-species cues. The vomeronasal neurons are thought to be highly selective in their responses. The tuning properties of individual receptors remain difficult to characterize due to the lack of a robust heterologous expression system. Here, we take a transgenic approach to ectopically express two Type 1 vomeronasal receptors in the mouse vomeronasal organ and characterize their responses to steroid compounds. We find that V1rj2 and V1rj3 are sensitive to two sulfated estrogens and can be activated by a broad variety of sulfated and glucuronidated steroids at high concentrations. Individual neurons exhibit narrow range of concentration-dependent activation. Collectively, a neuronal population expressing the same receptor covers a wide dynamic range in their responses to sulfated estrogens. These properties recapitulate the response profiles of endogenous neurons to sulfated estrogens.

  13. Tuning properties and dynamic range of type 1 vomeronasal receptors

    Science.gov (United States)

    Haga-Yamanaka, Sachiko; Ma, Limei; Yu, C. Ron

    2015-01-01

    The mouse vomeronasal organ (VNO) expresses chemosensory receptors that detect intra-species as well as inter-species cues. The vomeronasal neurons are thought to be highly selective in their responses. The tuning properties of individual receptors remain difficult to characterize due to the lack of a robust heterologous expression system. Here, we take a transgenic approach to ectopically express two type 1 vomeronasal receptors in the mouse VNO and characterize their responses to steroid compounds. We find that V1rj2 and V1rj3 are sensitive to two sulfated estrogens (SEs) and can be activated by a broad variety of sulfated and glucuronidated steroids at high concentrations. Individual neurons exhibit narrow range of concentration-dependent activation. Collectively, a neuronal population expressing the same receptor covers a wide dynamic range in their responses to SEs. These properties recapitulate the response profiles of endogenous neurons to SEs. PMID:26236183

  14. Human presynaptic receptors.

    Science.gov (United States)

    Schlicker, Eberhard; Feuerstein, Thomas

    2017-04-01

    Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release. Inhibitory autoreceptors represent a typical example of a negative feedback; they are tonically activated by the respective endogenous transmitter and/or are constitutively active. Autoreceptors also play a role under pathophysiological conditions, e.g. by limiting the massive noradrenaline release occurring during congestive heart failure. They can be used for therapeutic purposes; e.g., the α2-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. Heteroreceptors are presynaptic receptors at which transmitters from adjacent neurons, locally formed mediators (e.g. endocannabinoids) or hormones (e.g. adrenaline) can inhibit or facilitate transmitter release; they may be subject to an endogenous tone. The constipating effect of the sympathetic nervous system or of the antihypertensive drug clonidine is related to the activation of inhibitory α2-adrenoceptors on postganglionic parasympathetic neurons. Part of the stimulating effect of adrenaline on the sympathetic nervous system during stress is related to its facilitatory effect on noradrenaline release via β2-adrenoceptors.

  15. Controlling Population with Pollution

    Science.gov (United States)

    Browne, Joseph

    2010-01-01

    Population models are often discussed in algebra, calculus, and differential equations courses. In this article we will use the human population of the world as our application. After quick looks at two common models we'll investigate more deeply a model which incorporates the negative effect that accumulated pollution may have on population.

  16. Modeling Exponential Population Growth

    Science.gov (United States)

    McCormick, Bonnie

    2009-01-01

    The concept of population growth patterns is a key component of understanding evolution by natural selection and population dynamics in ecosystems. The National Science Education Standards (NSES) include standards related to population growth in sections on biological evolution, interdependence of organisms, and science in personal and social…

  17. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal;

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking...... similarities. Moreover, in some instances, antagonists for one receptor are able to inhibit the action of agonists for the respective other receptor. These observations suggest that there may be a functional or even physical interaction of both receptors. This article discusses potential mechanisms underlying...... the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1...

  18. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  19. Beyond the Receptor

    Institute of Scientific and Technical Information of China (English)

    Russell Jones

    2008-01-01

    @@ Had this Special Issue on plant hormones been published 5 years ago,it is likely that details about biosynthetic pathways would have taken center stage.As articles in this issue show,however,the field of plant hormone research has progressed rapidly and is now moving beyond the search for receptors.Progress in research on the mechanism of action of plant hormones has been rapid;receptors for the main classes of hormones have been identified;and the search is on for players downstream in signal-transduction chains.

  20. Biomimetic Receptors and Sensors

    Directory of Open Access Journals (Sweden)

    Franz L. Dickert

    2014-11-01

    Full Text Available In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs or molecular imprinting. The strategies are used for solid phase extraction (SPE, but preferably in developing recognition layers of chemical sensors.

  1. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou

    2005-01-01

    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  2. Distribution of estrogen and progesterone receptors in Epulis Fissuratum

    Directory of Open Access Journals (Sweden)

    Shahrabi Sh.

    2005-06-01

    Full Text Available Statement of Problem: Epulides Fissurata (EF are common proliferative and denture- induced lesions of the oral cavity with a predilection for female. This suggests a possible role for sex steroid hormones in the development and progression of these lesions. Purpose: The objective of this study was the immunohistochemical evaluation of epulis fissuratum of the oral cavity for estrogen and progesterone receptors expression in epithelial, stromal, inflammatory and endothelial cells populations. Materials and Methods: In this cross-sectional study, 15 samples of formalin- fixed, paraffin- embedded epulis fissuratums including marginal mucosal tissues in 4 cases as a control group, were immuno-histochemically evaluated for estrogen and progesterone receptors protein expression. Result: In 10 cases, estrogen receptor positivity was found within the epithelium and progesterone receptor immunoreactivity was present in 7 cases. Stromal cells exhibited estrogen and progesterone receptor immunostaining in many cases but only few cases showed expression of these receptors in the inflammatory and endothelial cells. Estrogen and progesterone receptors were also detected in some cases containing salivary glands tissue. Conclusion: Although chronic irritation may be the initiating factor for the occurence of epulis fissuratum, some of the cells in the lesion, could be potential targets for estrogen and progestrone hormones.

  3. Therapeutic Potential of 5-HT2C Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Nanna H. Jensen

    2010-01-01

    Full Text Available Serotonin 2C receptors are G protein-coupled receptors expressed by GABAergic, glutamatergic, and dopaminergic neurons. Anatomically, they are present in various brain regions, including cortical areas, hippocampus, ventral midbrain, striatum, nucleus accumbens, hypothalamus, and amygdala. A large body of evidence supports a critical role of serotonin 2C receptors in mediating the interaction between serotonergic and dopaminergic systems, which is at the basis of their proposed involvement in the regulation of mood, affective behavior, and memory. In addition, their expression in specific neuronal populations in the hypothalamus would be critical for their role in the regulation of feeding behavior. Modulation of these receptors has therefore been proposed to be of interest in the search for novel pharmacological strategies for the treatment of various pathological conditions, including schizophrenia and mood disorders, as well as obesity. More precisely, blockade of serotonin 2C receptors has been suggested to provide antidepressant and anxiolytic benefit, while stimulation of these receptors may offer therapeutic benefit for the treatment of psychotic symptoms in schizophrenia and obesity. In addition, modulation of serotonin 2C receptors may offer cognitive-enhancing potential, albeit still a matter of debate. In the present review, the most compelling evidence from the literature is presented and tentative hypotheses with respect to existing controversies are outlined.

  4. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown...

  5. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea;

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA......-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar...... limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e...

  6. P2-purinerge receptorer

    DEFF Research Database (Denmark)

    Solgaard, Marie; Jørgensen, Niklas Rye

    2005-01-01

    and by osteoclasts, and agonist binding affects cell proliferation, differentiation, activity and apoptosis. With increasing knowledge of the function and role of these receptors in bone biology, they will undoubtedly be a future target for the design of new drugs which can be used for treatment of metabolic bone...

  7. Androgen receptor mutations

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.W. Jenster (Guido); C. Ris-Stalpers (Carolyn); J.A.G.M. van der Korput (J. A G M); H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J. Trapman (Jan)

    1995-01-01

    textabstractMale sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. At least three pathological situations are associated wit

  8. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  9. Characterization of melanocortin receptors.

    Science.gov (United States)

    Goetz, Aaron S; Ignar, Diane M

    2003-11-01

    This unit describes a Scintillation Proximity Assay (SPA) for the measurement of ligand binding to melanocortin receptors (MCRs) using membranes prepared from cell lines stably expressing recombinant MCRs. It provides a facile method for determining the affinity of compounds at MC1R, MC3R, MC4R, or MC5R.

  10. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  11. 多巴胺受体2型基因-141C Ins/Del多态性与汉族精神分裂症的关联及连锁研究%Association of a Promoter Polymorphism in the Dopamine Receptor D2 Gene in Han Population with Schizophrenia

    Institute of Scientific and Technical Information of China (English)

    沈婷; 彭代辉; 肖玲; 王高华; 程自立; 藏德馨; 江开达

    2011-01-01

    Objective: To explore the association between a putative functional promoter polymorphism,-141C Ins/Del, in the dopamine receptor D2 gene and schizophrenia.Methods: The unrelated Han schizophrenic patients (n= 120) and Han control subjects (n=100) for the same polymorphism in Wuhan of Hubei province were investigated.The transmission disequilibrium test (TDT) was done in 35 core families of these schizophrenic patients.Results: The -141C Del allele frequency was significantly lower in patients than controls (P<0.05).The frequency of-141C Del was 11% in patients and 18% in control.Sixteen cases' parents had -141C Ins/Del genotype in the core families.By TDT analysis, 10 cases' parents passed the -141C Ins allele to their children,while 6 cases' parents passed -141C Del allele.There was no linkage from the analysis of the 35 families' data (P>0.05).Conclusion: The present and previous results may indicate that the -141C Ins/Del polymorphism of dopamine receptor D2 gene affects susceptibility to schizophrenia,and further studies need to be designed to explore the relationship in a larger population.%目的:探讨湖北武汉地区汉族人群中多巴胺受体D2型(D2)基因启动区-141位点胞嘧啶插入/缺失(-141C Ins/Del)多态性与精神分裂症的关联及连锁关系.方法:应用聚合酶链反应-限制性片段长度多态性方法,对120名精神分裂症患者、100名健康对照者进行基因分型,进而分析精神分裂症的-141CIns/Del多态性;对35个精神分裂症患者核心家系(患者及其生物学父母)的-141C Ins/Del进行了连锁不平衡分析.结果:多巴胺受体D2型基因启动区-141位点多态的等位基因、基因型频率在精神分裂症组与对照组之间的分布差异有显著性(P<0.05).在精神分裂症组中,-141C缺失的等位基因频率为0.11,对照组为0.18(比值比为0.55,95%可信区间为0.30-0.96,P<0.05).在35个核心家系中,16个患者父母的基因型为杂合子型"-141C

  12. Familial Risk for Major Depression is Associated with Lower Striatal 5-HT4 Receptor Binding

    DEFF Research Database (Denmark)

    Madsen, Karine; Torstensen, Eva; Holst, Klaus Kähler

    2015-01-01

    BACKGROUND: The 5-HT4 receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT4 receptor's in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study......-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). CONCLUSIONS: Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression...

  13. Molecular Population Genetics

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-01-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. PMID:28270526

  14. Population education country programmes.

    Science.gov (United States)

    1980-12-01

    Population education country programs in the countries of India, Malaysia, Nepal, the Philippines, and Sri Lanka are reviewed. In India the machinery is beginning to roll for the nationwide implementation of a 3-year national population education project. A variety of strategies will be used at the national and state levels using existing facilities and infrastructure for implementing various aspects of the program. Recommendations and proposed project activities arrived at during 2 workshop/training programs are outlined. The Malaysian population education program recently developed a working draft of the scope, content, and objectives of population education at the primary and lower and upper secondary levels. This working draft is being pretested among teachers and curriculum developers, and, once revised, it will serve as the overall guiding framework for those responsible for preparing curriculum and instructional materials on population education. The population education program in Nepal will be implemented by 3 units: Curriculum, Textbook, Supervision, and Development Center; Tribhuvan University; and Division of Adult Education. The longterm objective is to institutionalize population education in the formal and nonformal education programs including the university. The Population Education Program of the Philippines has prepared a reader in Filipino for grade 3 pupils. Population education in the country has been promoted to a lesser degree in private than in public schools. the Institutional Development Program of the Population Center Foundation conducted a Summer Institute in Instructional Product Development for the primary purpose of institutionalizing population in the social science curriculum at the tertiary level. The population education program of Sri Lanka will undergo a revival in the recently approved 2-year project agreement between Sri Lanka's government and the United Nations Fund for Population Activities.

  15. Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression.

    Science.gov (United States)

    Le Tulzo, Y; Shenkar, R; Kaneko, D; Moine, P; Fantuzzi, G; Dinarello, C A; Abraham, E

    1997-04-01

    The expression of proinflammatory and immunoregulatory cytokines rapidly increases in the lungs after hemorrhage, and such alterations contribute to the frequent development of acute inflammatory lung injury in this setting. Blood loss also produces elevations in catecholamine concentrations in the pulmonary and systemic circulation. In the present experiments, we used alpha- and beta-adrenergic receptor blockade to examine in vivo interactions between hemorrhage-induced adrenergic stimulation and pulmonary cytokine expression. Treatment of mice with the alpha-adrenergic receptor antagonist phentolamine prevented not only the elevation in mRNA levels of IL-1beta, TNF-alpha, and TGF-beta1, the increase in IL-1beta protein, but also the activation of nuclear factor (NF)-KB and cyclic AMP response element binding protein, which occurred in lung cells of untreated animals during the first hour after hemorrhage. In contrast, treatment before hemorrhage with the beta-adrenergic receptor antagonist propranolol was associated with increases in mRNA levels for IL-1beta, TNF-alpha, and TGF-beta1, which were greater than those present in untreated hemorrhaged mice, and did not prevent hemorrhage-associated increases in lung IL-1beta protein. Treatment with propranolol prevented hemorrhage-induced phosphorylation of cyclic AMP response element binding protein, but increased hemorrhage-associated activation of NF-KB. These results demonstrate that hemorrhage initially increases pulmonary cytokine expression through alpha- but not beta-adrenergic stimulation, and suggest that such alpha-adrenergic-mediated effects occur through activation of the transcriptional regulatory factor NF-kappaB.

  16. Binding of adrenergic ligands to liver plasma membrane preparations from the axolotl, Ambystoma mexicanum; the toad, Xenopus laevis; and the Australian lungfish, Neoceratodus forsteri.

    Science.gov (United States)

    Janssens, P A; Grigg, J A

    1988-09-01

    The beta-adrenergic ligand iodocyanopindolol (ICP) bound specifically to hepatic plasma membrane preparations from the axolotl, Ambystoma mexicanum (Bmax, 40 fmol/mg protein (P) at free concentration above 140 pM; KD, 42 pM); the toad, Xenopus laevis (Bmax, 200 fmol/mg P at 1 nM; KD, 300 pM); and the Australian lungfish, Neoceratodus forsteri (Bmax, 100 fmol/mg P at 5 nM). For the lungfish, the Scatchard plot was curved showing two classes of binding site with KD's of 20 and 500 pM. Neither the alpha 1-adrenergic ligand prazosin nor the alpha 2-adrenergic ligand yohimbine bound specifically to hepatic membrane preparations from any of the three species. Several adrenergic ligands displaced ICP from hepatic membrane preparations of all three species with KD's of Axolotl--propranolol, 50 nM; isoprenaline, 600 nM; adrenaline, 10 microM; phenylephrine, 20 microM; noradrenaline, 40 microM; and phentolamine, greater than 100 microM; X. laevis--propranolol, 30 nM; isoprenaline, 100 microM; adrenaline, 200 microM; noradrenaline, 300 microM; phenylephrine, 1 mM; and phentolamine, greater than 1 mM; N. forsteri,--propranolol, 25 nM; isoprenaline, 1 microM; adrenaline, 20 microM; phenylephrine, 35 microM; noradrenaline, 600 microM; and phentolamine, 400 microM. These findings suggest that alpha-adrenergic receptors are not present in hepatic plasma membrane preparations from these three species and that the hepatic actions of catecholamines are mediated via beta-adrenergic receptors. The order of binding of the beta-adrenergic ligands suggests that the receptors are of the beta 2 type.

  17. Histamine H3-receptor isoforms.

    Science.gov (United States)

    Bakker, R A

    2004-10-01

    Increasing evidence supports a role for HA as a neurotransmitter and neuromodulator in various brain functions, including emotion, cognition, and feeding. The recent cloning of the histamine H3 receptor allowed for the subsequent cloning of a variety of H3 receptor isoforms from different species as well as the H4 receptor. As a result a wide variety of H3-receptor isoforms are now known that display differential brain expression patterns and signalling properties. These recent discoveries are discussed in view of the growing interest of the H3 receptor as a target for the development of potential therapeutics.

  18. Levamisole receptors: a second awakening

    Science.gov (United States)

    Martin, Richard J.; Robertson, Alan P.; Buxton, Samuel K.; Beech, Robin N.; Charvet, Claude L.; Neveu, Cedric

    2012-01-01

    Levamisole and pyrantel are old (1965) but useful anthelmintics that selectively activate nematode acetylcholine ion-channel receptors; they are used to treat roundworm infections in humans and animals. Interest in their actions has surged, giving rise to new knowledge and technical advances, including an ability to reconstitute receptors that reveal more details of modes of action/resistance. We now know that the receptors are plastic and may form diverse species-dependent subtypes of receptor with different sensitivities to individual cholinergic anthelmintics. Understanding the biology of the levamisole receptors is expected to inform other studies on anthelmintics (ivermectin and emodepside) that act on ion-channels. PMID:22607692

  19. Befolkningsudviklingen (Population Development)

    DEFF Research Database (Denmark)

    Nørgaard, Jørgen

    2010-01-01

    The article takes the 1972 report, The Limits to Growth as its starting point, briefly explaining the Systam Dynamics model used for the report's analyses. Focus is on the important role of population. The simple model of I = PxAxT, where I is the environmental Impact, P population, A is the Affl......The article takes the 1972 report, The Limits to Growth as its starting point, briefly explaining the Systam Dynamics model used for the report's analyses. Focus is on the important role of population. The simple model of I = PxAxT, where I is the environmental Impact, P population...

  20. Measurably evolving populations

    DEFF Research Database (Denmark)

    Drummond, Alexei James; Pybus, Oliver George; Rambaut, Andrew

    2003-01-01

    processes through time. Populations for which such studies are possible � measurably evolving populations (MEPs) � are characterized by sufficiently long or numerous sampled sequences and a fast mutation rate relative to the available range of sequence sampling times. The impact of sequences sampled through...... time has been most apparent in the disciplines of RNA viral evolution and ancient DNA, where they enable us to estimate divergence times without paleontological calibrations, and to analyze temporal changes in population size, population structure and substitution rates. Thus, MEPs could increase our...